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Carbohydrates as Organic Raw Materials V Building a Sustainable Future
Lisbon – Portugal FCUL 20-23 JANUARY 2009
CCOONNTTEENNTTSS Welcome…………………………………………………………………………...… 1Commission of Honour……………………………………………………………... 1Scientific Committee………………………………………………………………… 3Conference Awards…………………………………………………………………. 3Organizing Committee……………………………………………………...………. 4Acknowledgements………………………………………………...……………….. 6Sponsors…………………………………………………………...………………… 7Conference Media……………………………………………………………..……. 10Previous CORM Meetings…………………………………………………..……… 11General Information……………………………………………………….………... 11
Meeting Venue…………………..…………………………..………………... 11How to reach FCUL…………………………………………………………... 12Registration and Information Desk………………………………………….. 12Lunch……………….…………………………………………………………... 12Communication Network Rooms……………………………………………. 12
Social Programme (Included in the Registration Fee)……………..……………. 13Brokerage Event……..…………………………………………………………….... 13Programme Schedule……………………………………………….……………… 14Scientific Information………………………………………………..………………. 14
Slide Preview Room………………………………………………….……..… 14Posters……………………………………………………………………….… 14Scientific Programme Schedule………………………………………….….. 15
Scientific Programme………………………………….………………………….... 16Invited Lectures………………………………...….………………………….. 24Oral Communications……………………….....……………………………... 26Poster Presentations……………………….…………………………………. 28
Abstracts………………………………..……………………………………………. 35Invited Lectures……………………………………………………………..… 37Oral Communications……………………………………….………………... 69Poster Presentations……………………….……………………………….… 85
Author Index…………………………………………………………………………. 148List of Participants…………………………………………………………...……… 155
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WWEELLCCOOMMEE The Organizing Committee cordially welcomes all participants and accompanying persons to Lisbon for the meeting “Carbohydrates as Organic Raw Materials V – Building a Sustainable Future” which is to be held at the Faculdade de Ciências da Universidade de Lisboa. CCOOMMMMIISSSSIIOONN OOFF HHOONNOOUURR Presided over by his Excellency the President of the Portuguese Republic Prof. Doutor Aníbal Cavaco Silva
Minister of the Environment and Territorial Planning and Regional Development Prof. Doutor Francisco Nunes Correia
Minister of Economy and Innovation Doutor Manuel de Almeida de Pinho
Minister of Science, Technology and Higher Education Prof. Doutor José Mariano Gago
Minister of Parliament Affairs Prof. Doutor Augusto Santos Silva
Ambassador of France in Portugal Dr. M. Denis Delbourg
Secretary of State for Science, Technology and Higher Education Prof. Doutor Manuel Heitor
Secretary of State for Tourism Dr. Bernardo Trindade
Mayor of the City of Lisbon Dr. António Costa
Mayor of the City of Alpiarça Dra. Vanda Nunes
Governor of Lisbon Dra. Dalila Araújo
Governor of Santarem Dr. Paulo Fonseca
President of Tourism of Lisbon and Tagus Valley Dr. Joaquim Luís Rosa do Céu
President of the Engineers Association Eng.º Fernando Ferreira Santo
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Dean of the Universidade de Lisboa Prof. Doutor António Sampaio da Nóvoa
Dean of the Universidade Técnica de Lisboa Prof. Doutor Fernando Ramôa-Ribeiro
Vice Dean of the Universidade de Lisboa and Coordinator of Oficina de Transferência de Tecnologia da Universidade de Lisboa Prof. Doutor António Gomes de Vallêra
President of Fundação para a Ciência e a Tecnologia Prof. Doutor João José dos Santos Sentieiro
President of Agência de Inovação Dr. Lino Fernandes
President of Instituto Nacional de Saúde Dr. Ricardo Jorge Prof. Doutor José Manuel Pereira Miguel
President of Instituto Nacional de Engenharia, Tecnologia e Inovação Prof. Doutora Teresa Ponce de Leão
President of Instituto de Tecnologia Química e Biológica Prof. Doutor José Artur Martinho Simões
President of Sociedade Portuguesa de Química Prof. Doutor José Luís Figueiredo
President of Grupo Espanhol de Carbohidratos Prof. Doutor Ramon Estevez
President of Bial Dr. Luís Portela
President of Portucel Dr. Pedro Queirós Pereira (will be represented by Prof. Doutor Serafim Tavares)
President of the National Association of Technical Engineers Eng.º Augusto Ferreira Guedes
President of Faculdade de Ciências da Universidade de Lisboa Prof. Doutor Nuno Manuel Guimarães
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SSCCIIEENNTTIIFFIICC CCOOMMMMIITTTTEEEE
Berit Paulsen, president of ICS, Norway
Bernardo Herold, Portugal
Derek Horton, USA
Fernando Ramôa Ribeiro, Portugal
Fons Voragen, The Netherlands
Francesco Nicotra, Italy
Gerard Descotes, France
Herman van Bekkum, The Netherlands
Hugues Driguez, Grenoble, France
Jacques Defaye, France
Joachim Thiem, Germany
Laurence Mulard, France
Michel Guisnet, France
Otto Holst, president of ECO, Germany
Patrick Rollin, France
Paul Kosma, Austria
Pierre Sinaÿ, France
Werner Praznik, Austria
CCOONNFFEERREENNCCEE AAWWAARRDDSS The Scientific Committee will select 3 posters to be awarded a prize and also a young researcher award will be given from among the poster and oral communication authors.
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OORRGGAANNIIZZIINNGG CCOOMMMMIITTTTEEEE Amélia Pilar Rauter, Lisbon Chairperson Yves Queneau, Lyon Chairperson Frieder W. Lichtenthaler, Darmstadt
Honorary Chairperson
Alice Martins, CQB-FCUL
Ana Paula Carvalho, DQB-FCUL
Ana Paula Esteves, DQ-Uminho
Ana Paula Paiva, DQB-FCUL
Carlos Borges, DQB-FCUL
Carlos Lajas - Agência de Inovação
Carlos Noeme, ISA-UTL
Christopher Maycock, DQB-FCUL
Estrela Melo Jorge, DQB-FCUL
Fernando Santos, CQB-FCUL
Filipa V. M. Silva, CQB-FCUL/ESAS-IPS
Filomena Martins - DQB-FCUL
Isabel Ismael, UBI
João Bordado, IST-UTL
Jorge Justino, ESAS-IPS
Júlia Costa, ITQB-UNL
Luísa Bívar Roseiro, INETI
Madalena Humanes, DQB-FCUL
Margarida Goulart, ITN
Margarida Meireles, DQB-FCUL
Maria Eduarda Araújo, DQB-FCUL
Maria Soledade Santos, DQB-FCUL
Susana Pina dos Santos, DQB-FCUL
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Students Ana Catarina Araújo
Ana Rita Jesus
Catarina Spúlveda
Daniela Batista
Filipa Marcelo
Filipa Siopa
Hugo Gameiro
Joana Almeida
Joana Salta
João Pedro Pais
João Sardinha
Luís Miguel Carvalho
Mafalda Soares Fatela
Manuel Silva
Maria Emília Vedor
Nuno Manuel Xavier
Nuno Neng
Paulo Amorim Madeira
Rocio Campoy
Susana Cristina Marques
Susana Dias Lucas
Vasco Miguel Cachatra
Secretariat
Leonor Rodrigues / Béatrice Huberty
Conselho Directivo, FCUL Ed. C5, 4 º Piso, 1749-016 Lisboa Portugal Tel: +351 217 500450 Fax: +351 21 7500115 E-mail: [email protected] Web Address: http://cormv.fc.ul.pt
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AACCKKNNOOWWLLEEDDGGMMEENNTTSS Ambassade de France
AMSLab
ANET
Banco Espirito Santo
BRUKER
Cafés Delta
Caixa Geral de Depósitos
Câmara Municipal de Alpiarça
CNRS Department Energy and Sustainable Development
CNRS Department of Chemistry
CTT
Dan Cake
Dias de Sousa, S.A.
Dionex
ESAS – Escola Superior Agrária de Santarém
FCUL – Faculdade de Ciências da Universidade de Lisboa
Fermentec
F. Hoffmann-La Roche Ltd
Fundação para a Ciência e a Tecnologia
FLAD – Fundação Luso-Americana para o Desenvolvimento
GalChimia
Governo Civil do Distrito de Santarém
IZASA S.A.
Júlio Logrado Figueiredo Lda.
LaborSpirit
Livraria Escolar Editora
Lusa- Agência de Notícias de Portugal S.A.
Papelaria Desportiva
Portucel/Soporcel
Qlabo
Rádio Clube Português
Rádio e Televisão de Portugal
UNICAM
UNICER
Turismo de Lisboa
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SSPPOONNSSOORRSS
Ambassade de France
AMSLab
ANET
Banco Espirito Santo
BRUKER
Cafés Delta
Câmara Municipal de Alpiarça
CNRS Department Energy and Sustainable Development as sponsor of the meeting, and CNRS Department of Chemistry, who support financially some participants for attending the meeting. http://www.cnrs.fr
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CTT
Dan Cake
Dias de Sousa, S.A.
Dionex
ESAS – Escola Superior Agrária de Santarém
Faculdade de Ciências da Universidade de Lisboa
Fermentec
F. Hoffmann-La Roche Ltd
Fundação para a Ciência e a Tecnologia
Fundação Luso-Americana para o Desenvolvimento (FLAD)
GalChimia
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Governo Civil do Distrito de Santarém
IZASA SA
LaborSpirit
Livraria Escolar Editora
Papelaria Desportiva
Portucel/Soporcel
Qlabo
Sociedade Portuguesa de Química
UNICAM - Sistemas Analíticos, Lda.
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UNICER
Turismo
CCOONNFFEERREENNCCEE MMEEDDIIAA
Lusa - Agência de Notícias de Portugal S.A.
Rádio Clube Português
RTP
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PPRREEVVIIOOUUSS CCOORRMM MMEEEETTIINNGGSS CORM I, Darmstadt (1990), chaired by Prof. Lichtenthaler.
CORM II, Lyon (1992), chaired by Prof. Descotes.
CORM III, Wageningen (1994), chaired by Prof. van Bekkum and Prof. Voragen.
CORM IV, Wien (1997), chaired by Prof. Praznick.
GGEENNEERRAALL IINNFFOORRMMAATTIIOONN Meeting Venue The Meeting “Carbohydrates as Organic Raw Materials V – Building a Sustainable Future” will take place at Faculdade de Ciências da Universidade de Lisboa (FCUL), Campo Grande, Lisbon, Portugal, starting on the 20th of January and ending on the 23rd. of January, 2009. Registration and the Sessions on the 20th of January will take place in building C3 (room 3.2.14), and from Wednesday to Friday all the sessions will take place in building C6 (room 6.1.36).
Access to the Buildings
Access to the Buildings
C3- Registration Opening Ceremony
C6- Sessions 21-23 January
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How to reach FCUL Lisbon Airport is located in the city and the best way to reach FCUL or the hotels indicated in the accommodation form is to take a taxi (7.5 – 10 €). There are also buses (Carris) to the centre with connection by subway to FCUL (subway Campo Grande followed by 5min. walk to FCUL or with connection to the hotels. For the subway you need to buy a reusable card for 0.5 € and then each journey will cost 0.8 € or you can choose to charge the card with a one day ticket for subway and buses (Metro/Carris) for 3.70€. Registration and Information Desk Registration will take place in the foyer of building C3. For the remaining days the Information Desk will be located in Building C6. C3 Tuesday, January 20 12:00 – 18:30 C6 Wednesday, January 21 8:30 – 18:30 C6 Thursday, January 22 8:30 – 15:30 C6 Friday, January 23 9:30 – 18:00 Lunch Lunch will be served in Building C6 and is included in the registration fee from Wednesday, January 21 until Friday, January 23. We kindly ask you to present your lunch tickets. Communication Network Rooms FCUL IT Center has made available the following temporary login for the wireless Academic Network (eduroam)
Username: [email protected] Password: w1r3le55 Network name SSID: eduroam. Please use WPA/TKIP and PEAP. More info at http://wireless.ul.pt or connect to ‘eduoroam-guest’ wireless network and visit the link above. The same username and password should be used for network access in the room 5.2.25A, located in Building C5. Language English will be the official language of the Conference.
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Voltage In Portugal the line voltage is 220 V. Insurance Participants are responsible for arranging their own health and accident insurance. Banking Several banks are located near the FCUL. Most restaurants and shops will accept credit cards. Changing Currency There are facilities to change foreign currency at Lisbon Airport and in downtown Lisbon (Baixa area – subway station Restauradores) Climate Temperatures are expected to be arround 10 ºC. SSOOCCIIAALL PPRROOGGRRAAMMMMEE (Included in the Registration Fee) Tuesday, January 20 19:00 Welcome Cocktail at the French Ambassy
Residence offered by his Excellency The Ambassador Denis Delbourg.
Thursday, January 22 15:30 Excursion to Alpiarça, visit to the Museu dos Patudos, wine tasting and Conference Dinner.
BBRROOKKEERRAAGGEE EEVVEENNTT This event, organized under the auspices of Agência de Inovação, will foster communication between the participants of the meeting focusing on development of joint projects and technical cooperation.
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PPRROOGGRRAAMMMMEE SSCCHHEEDDUULLEE
Time Tuesday Wednesday Thursday Friday
08:30 – 09:00
09:00 – 09:30
09:30 – 10:00
Scientific Programme
Scientific Programme
10:00 – 10:30 Coffee break Coffee break
10:30 – 11:00
Scientific Programme
11:00 – 11:30 Coffee break
11:30 – 12:00
12:00 – 12:30
Scientific Programme
12:30 – 13:00
Scientific Programme
Scientific Programme
13:00 – 14:00 Lunch
Lunch Lunch
14:00 – 14:30
14:30 – 15:00
Registration
15:00 – 15:30
Scientific Programme
Brokerage Event
15:30 –16:00
Opening/Scientific Programme
Scientific Programme
16:00 – 16:30 Coffee break Coffee break
Scientific Programme
16:30 – 17:00 Coffee break
17:00 – 17:30
17:30 – 18:00
Scientific Programme/Closure
18:00 – 18:30
Scientific Programme
Scientific Programme
18:30 – Welcome Cocktail
Excursion
and
Conference Dinner
SSCCIIEENNTTIIFFIICC IINNFFOORRMMAATTIIOONN Presentation Preview Room Speakers are kindly asked to contact the secretariat for their presentation preview 24 h before their lecture/oral communication (room 6.2.52). Posters Posters will be displayed during the whole conference in the hall of C6. Authors are required to display their own posters on the boards provided on tuesday, before the opening session. Material to attach posters will be available. The poster session will take place on thursday from 14:00 to 15:30 and 3 posters will be selected to be awarded by the scientific committee.
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SSCCIIEENNTTIIFFIICC PPRROOGGRRAAMMMMEE SSCCHHEEDDUULLEE
Time Tuesday Wednesday Thursday Friday
08:30 – 09:00
Chairpersons: P.Kosma
M. J. Calhorda IL6 M. Moser
Chairperson: G.Descotes
IL16 M. Philippe
09:00 – 09:30 IL7 S. Jarosz IL17 T. Benvegnu
09:30 – 09:45 OC1 OC11
09:45 – 10:00 OC2 OC12
Chairpersons: L. A. Mulard V. Soares
IL22 S. Oscarson
10:00 – 10:30 Coffee break Coffee break IL23 R. Woods
10:30 – 10:45 OC15
10:45 – 11:00
Chairpersons: F. Nicotra C. Castro
IL8 S. Penades
Chairpersons: J. Thiem C. Lopez
IL18 H.P. Wessel OC16
11:00 – 11:30 IL9 S. Kitamura IL19 A. Marra Coffee break
11:30 – 12:00 IL10 G. Fernandez IL20 B. M. Pinto
Chairpersons: J. Defaye
F. Santoyo IL24 C. Bruggink
12:00 – 12:15 OC3
12:15 – 12:30 OC4 IL21 V. Kren IL25 R. Rastall
12:30 – 12:45 OC13
12:45 – 13:00 OC14 IL26 C. O. Mellet
13:00 – 14:00
Lunch
Lunch Lunch
14:00 – 14:30
Chairpersons: B. Paulsen
F. Fernandes IL11 P. Vogel
Chairpersons: O. Holst B. Herold
IL27 J. Vliegenthart
14:30 – 14:45
14:45 – 15:00
Registration
IL12 C. Portella IL28 K. Ágoston
15:00 – 15:15 OC5
15:15 – 15:30 Opening Session
OC6
Poster Session
and
Brokerage Event
IL29 A. Striegel
15:30 – 16:00 Chairperson:
F. Lichtenthaler IL1 S. Perez
IL13 J. P. Leal IL30 F. Quignard
16:00 – 16:30 Coffee break Coffee break IL31 D. Samain
16:30 – 17:00
Chairpersons: R. Estevez L. Abrantes
IL2 P. Fuertes
Chairpersons: P. Rollin
H. Florêncio IL14 D. Ferreira
Coffee break
17:00 – 17:30 IL3 J. Galbis IL15 M. Coimbra Chairperson: Y.Queneau
IL32 F. Lichtenthaler
17:30 – 17:45 OC7
17:45 – 18:00 IL4 H. Amorim
OC8
Euroglycosciences Forum Presentation
Closure
18:00 – 18:15 OC9
18:15 – 18:30 IL5 L. S. M. Bento
OC10
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SSCCIIEENNTTIIFFIICC PPRROOGGRRAAMMMMEE The Scientific Programme consists of invited lectures, oral communications and poster presentations focused on the contribution of carbohydrates as raw materials for food and pharmaceutical industries, cosmetics, agrochemistry and fibers. Subjects dealt with in the follow-up sessions will include: A. Food B. Detergency and cosmetics C. Pharmaceuticals D. Agrochemicals E. Fibers and paper F. Synthesis and catalysis G. Materials and processes H. Biotechnology I. Others Tuesday, January 20, 2009
15:00 Opening Ceremony
Chairperson: Frieder Lichtenthaler
15:30 IL1 BACK TO THE BIO-FUTURE Serge Pérez, CERMAV-CNRS, France
16:00 Coffee Break
Chairpersons: Ramon Estevez and Luísa Abrantes
16:30
IL2 BIOHUB® PROGRAM FOR THE DEVELOPMENT OF NEW CEREAL-BASED BIO-REFINERIES
Patrick Fuertes, Roquette, France
17:00 IL3 NEW BIODEGRADABLE AND FUNCTIONAL POLYMERS FROM EASILY AVAILABLE SUGARS Juan A. Galbis, University of Seville, Spain
17:30
IL4 CARBOHYDRATES FOR ETHANOL AND DISTILLED BEVERAGES Henrique Amorim, Fermentec, Brazil
18:00 IL5 ADVANTAGES IN PROCESSING WHITE SUGAR WHEN SUGAR FACTORIES ARE ASSOCIATED WITH AN ETHANOL PLANT Luis S.-M. Bento, Sucropedia, Portugal
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Wednesday, January 21, 2009
Chairpersons: Paul Kosma and Maria-José Calhorda
8:30 IL6 SUCROSE – A PROSPERING AND SUSTAINABLE ORGANIC RAW MATERIAL Matthias Moser, Südzucker, Germany
9:00 IL7 WHAT CAN BE DONE FROM SUCROSE? TOWARDS MACROCYCLIC RECEPTORS WITH SUCROSE SCAFFOLD Slawomir Jarosz, Polish Academy of Sciences, Poland
9:30 OC1 DESIGN OF AMPHIPHILIC CATALYSTS FOR THE SELECTIVE CONVERSION OF SUGARS François Jérôme, Nicolas Villandier, Ayman Karam, Joël Barrault, Ronan Pierre, Yves Queneau,CNRS-Université de Poitiers, France
9:45 OC2 A DUAL PURPOSE IMMOBILIZED BIOCATALYST FOR INULIN AND SUCROSE HYDROLYSIS Pedro Fernandes, Marco P.C. Marques, Stefano Cattorini, Filipe Carvalho, J.M.S. Cabral, Instituto Superior Técnico, Portugal
10:00 Coffee Break
Chairpersons: Francesco Nicotra and Carlos Castro
10:30 IL8 GLYCONANOMATERIALS AND APPLICATIONS Soledad Penadés, CIBER-BBN, Spain
11:00 IL9 LINEAR AND CYCLIC AMYLOSES: BEYOND NATURAL Shinichi Kitamura, Osaka Prefecture University, Japan
11:30 IL10 CYCLODEXTRINS IN NANOMEDICINE: RATIONAL DESIGN OF DRUG DELIVERY SYSTEMS, GENE VECTORS AND ANTITOXINS José M. García Fernández, Carmen Ortiz Mellet, Jacques Defaye, Pierre Vierling, CSIC-University of Seville, Spain
12:00 OC3 SELF-ASSEMBLIES OF AMPHIPHILIC CYCLODEXTRINS F. Djedaïni-Pilard, V. Bonnet, M. Roux, B. Perly, Université de Picardie-Jules Verne, France
12:15 OC4 EFFICIENT TELOMERISATION OF BUTADIENE WITH STARCH Julien Mesnager, Anne Lambin, Claude Quettier, Catherine Pinel, Université de Lyon, France
12:30 Lunch
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Wednesday, January 21, 2009
Chairpersons: Berit Paulsen and Fernando Fernandes
14:00 IL11 DRUGS AND HIGH-VALUE-ADDED MATERIALS FROM AGRICULTURAL LEFTOVERS Pierre Vogel, Swiss Federal Institute of Technology in Lausanne, Switzerland
14:30 IL12 FROM HEMICELLULOSE-DERIVED PENTOSES TO MULTIFUNCTIONAL BUILDING BLOCKS Charles Portella, Richard Plantier-Royon, Ariane Bercier, Sophie Goumain, Université de Reims Champagne-Ardenne, France
15:00 OC5 SYNTHESIS OF ACIDIC XYLOOLIGOMER MODEL COMPOUNDS Wilhelm Herok, Beatriz Abad-Romero, Georg Sixta, Clemens Gruber, Herbert Sixta, Paul Kosma, University of Natural Resources and Applied Life Sciences, Austria
15:15 OC6 POLYSACCHARIDES WITH REACTIVE CARBONYLS: CHEMICAL AND PHYSICAL PROPERTIES Bjørn E. Christensen, Kåre A. Kristiansen, NOBIPOL, Norway
15:30 IL13 CARBOHYDRATES AND RADIATION: TOGETHER THEY WORK M. H. Casimiro, J. P. Leal, CQB-FCUL, Universidade de Lisboa, Portugal
16:00 Coffee Break
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Wednesday, January 21, 2009
Chairpersons: Patrick Rollin and Helena Florêncio
16:30 IL14 HOW CARBOHYDRATE RESEARCH SUPPORTS LOCAL AGRO-FOOD PRODUCTION Dulcineia Ferreira, Agricultural Polytechnic School of Viseu, Portugal
17:00 IL15 OLIVE POMACE BIOREFINERY – CONTRIBUTION OF POLYSACCHARIDES Manuel A. Coimbra, Susana M. Cardoso, José A. Lopes-da-Silva, University of Aveiro, Portugal
17:30 OC7 SUGARS AND LIGNOSULFONATES RECOVERY FROM SULFITE PULPING OF EUCALYPTUS GLOBULUS BY THE APPLICATION OF MEMBRANE SEPARATION PROCESSES José Augusto Restolho, António Prates, Maria-Norberta de Pinho, Maria D. Afonso, Instituto Superior Técnico, Portugal
17:45 OC8 OXIDATION OF CELLULOSE FROM KRAFT PULP J. A. Figueiredo, Ana Paula Duarte, Suzana Martins, Carla Abrantes, M. Isabel Ismael, Rogério Simões, Universidade da Beira Interior, Portugal
18:00 OC9 THE PROS AND CONS OF THE DEDICATED UPGRADE OF THE HEMICELLULOSIC SUGAR STREAM IN A BIOREFINERY FRAMEWORK Luís C. Duarte, Florbela Carvalheiro, Talita S. Fernandes, Francisco M. Gírio, INETI, Portugal
18:15 OC10 NOVEL POLYAMIDES FROM DISACCHARIDE-DERIVED DICARBOXYLIC ACIDS Eckehard Cuny, Frieder W. Lichtenthaler, Technische Universität Darmstadt, Germany
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Thursday, January 22, 2009
Chairperson: Gérard Descotes
8:30 IL16 GREEN CHEMISTRY FOR SUSTAINABLE DEVELOPMENT AT L’OREAL: SYNTHESIS OF NEW C-GLYCOSIDES OF LARGE INTEREST IN COSMETICS Michel Philippe, L’Oreal, France
9:00 IL17 GREEN SUGAR-BASED SURFACTANTS AND MONOMERS FROM MARINE RESOURCES Thierry Benvegnu, M. Roussel, D. Plusquellec, J.-F. Sassi, H. Le Deit, J. Hendrickx, Y. Lerat, Ecole Nationale Supérieure de Chimie de Rennes, France
9:30 OC11 ISOSORBIDE: A “SUSTAINABLE DIOL” DERIVED FROM SORBITOL FOR THE SYNTHESIS OF NEW AMPHIPHILES Valérie Molinier, Ying Zhu, Morgan Durand, Jean-Marie Aubry, Ecole Nationale Supérieure de Chimie de Lille, France
9:45 OC12 AN INNOVATIVE AND OPTIMIZED SOL GEL IMMOBILIZATION TECHNIQUE FOR GLYCOSIDES ENZYMATIC HYDROLYSIS Helder Vila-Real, António J. Alfaia, António T.Calado, Maria H.L. Ribeiro, Universidade de Lisboa, Portugal
10:00 Coffee Break
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Thursday, January 22, 2009
Chairpersons:Joachim Thiem and Cristóbal López
10:30 IL18 CARBOHYDRATES IN PHARMACEUTICAL INDUSTRIES Hans Peter Wessel, F. Hoffmann La Roche, Switzerland
11:00 IL19 CALIXARENE-BASED GLYCOSIDE CLUSTERS AS POTENTIAL ANTIVIRAL DRUGS Alberto Marra, Università di Ferrara, Italy
11:30 IL20 BACK TO MY ROOTS: NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF TYPE-2 DIABETES FROM AN ANCIENT HERBAL REMEDY B. Mario Pinto, Simon Fraser University, Canada
12:00 IL21 BIOPROCESSING OF NATURAL PRODUCTS WITH GLYCOSIDASES Vladimír Kren, Lenka Weignerová, Petr Marhol, Czech Academy of Sciences, Czech Republic
12:30 OC13 ENGINEERING TRANSGLUCOSIDASES REGIOSPECIFICITY FOR PROGRAMMED CHEMO-ENZYMATIC SYNTHESIS OF COMPLEX BACTERIAL CARBOHYDRATES E. Champion, J. Boutet, K. Descroix, C. Moulis, S. Morel, P. Monsan, L. A. Mulard, M. Remaud-Siméon, Isabelle André, Université de Toulouse, France
12:45 OC14 CARBOHYDRATE – LECTIN INTERACTIONS: PROBING MULTIVALENCY WITH TOPOLOGICALLY DEFINED GLYCOCALIX[4]ARENES Samy Cecioni, S. Vidal, S. E. Matthews, A. Imberty, J.-P. Praly, Université Claude Bernard Lyon 1, France
13:00 Lunch
14:00 Poster Session Brokerage Event
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Friday, January 23, 2009
Chairperson: Laurence A. Mulard, V. Soares
9:30 IL22 THE USE OF MICROBIAL POLYSACCHARIDES AS VACCINES - POSSIBILITIES, PROBLEMS AND PROSPECTS Stefan Oscarson, University College Dublin, Ireland
10:00 IL23 COMPUTATIONALLY-GUIDED GLYCOSCIENCE: TOWARD THE RATIONAL DEVELOPMENT OF CARBOHYDRATE-BASED ANTI-VIRAL THERAPEUTICS Robert J. Woods, University of Georgia, USA
10:30 OC15 NOVEL DI-BRANCHED MONOSACCHARIDES AND IMINO SUGARS K. V. Booth, G. W. J. Fleet, University of Oxford, United Kingdom
10:45 OC16 SYNTHETIC APPROACHES TO NOVEL THIOSUGAR SCAFFOLDS CONTAINING α,β-UNSATURATED CARBONYL FUNCTIONS Nuno M. Xavier, Amélia P. Rauter, CQB-FCUL, Universidade de Lisboa, Portugal
11:00 Coffee Break
Chairpersons:Jacques Defaye and Francisco Santoyo
11:30 IL24 CARBOHYDRATE-ANALYSIS: LIQUID CHROMATOGRAPHY TO SOLVE A CHALLENGE Cees Bruggink, and Detlef Jensen, Dionex Benelux BV, The Netherlands
12:00 IL25 FUNCTIONAL FOOD INGREDIENTS FOR GUT HEALTH: EXPLOITATION OF PLANT BIOMASS SOURCES FOR NOVEL INGREDIENTS Robert Rastall, The University of Reading, United Kingdom
12:30 IL26 DIFRUCTOSE DIANHYDRIDE-ENRICHED CARAMELS: PREBIOTIC AND NUTRACEUTICAL PROPERTIES Carmen Ortiz Mellet, Julio Gálvez, Antonio Zarzuelo, Raquel Ruiz, Luis A. Rubio,José M. García Fernandez, University of Seville, Spain
13:00 Lunch
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Friday, January 23, 2009
Chairpersons: Otto Holst and Bernardo Herold
14:00 IL27 STUDIES ON THE STRUCTURE OF POLYSACCHARIDES Johannes F.G. Vliegenthart, Utrecht University, The Netherlands
14:30 IL28 COMMERCIALIZATION MODELS OF POTENTIAL GLYCOPRODUCTS Károly Ágoston, Inge Lundt, Joachim Thiem, Arnold Stütz, István Bajza, Lars Kröger, Gyula Dékány, Glycom A/S, Denmark
15:00 IL29 INFLUENCE OF ANOMERIC CONFIGURATION AND GLYCOSIDIC LINKAGE ON THE SOLUTION CONFORMATIONAL ENTROPY OF OLIGOSACCHARIDES André M. Striegel, Florida State University, USA
15:30 IL30 MARINE POLYSACCHARIDES AEROGELS: MATERIALS FOR CATALYSIS AND ADSORPTION Françoise Quignard, Institut Charles Gerhardt, France
16:00 IL31 POLYSACCHARIDES TRANSFORMATION, NEW PROCESSES AND TECHNOLOGIES Camélia Stinga, David Guérin, Daniel Samain, CERMAV-CNRS, France
16:30 Coffee Break
Chairperson: Yves Queneau
17:00 IL32 CARBOHYDRATES AS ORGANIC RAW MATERIALS : THE MAJOR CHALLENGES AHEAD Frieder W. Lichtenthaler, Technische Universität Darmstadt, Germany
17:30 Euroglycosciences Forum Closing Ceremony
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IINNVVIITTEEDD LLEECCTTUURREESS IL1 BACK TO THE BIO-FUTURE
Serge Pérez
IL2 BIOHUB® PROGRAM FOR THE DEVELOPMENT OF NEW CEREAL-BASED BIO-REFINERIES
Patrick Fuertes
IL3 NEW BIODEGRADABLE AND FUNCTIONAL POLYMERS FROM EASILY AVAILABLE SUGARS Juan A. Galbis
IL4 CARBOHYDRATES FOR ETHANOL AND DISTILLED BEVERAGES Henrique Amorim
IL5 ADVANTAGES IN PROCESSING WHITE SUGAR WHEN SUGAR FACTORIES ARE ASSOCIATED WITH AN ETHANOL PLANT Luis San Miguel Bento
IL6 SUCROSE – A PROSPERING AND SUSTAINABLE ORGANIC RAW MATERIAL Matthias Moser
IL7 WHAT CAN BE DONE FROM SUCROSE? TOWARDS MACROCYCLIC RECEPTORS WITH SUCROSE SCAFFOLD Slawomir Jarosz
IL8 GLYCONANOMATERIALS AND APPLICATIONS Soledad Penadés
IL9 LINEAR AND CYCLIC AMYLOSES: BEYOND NATURAL Shinichi Kitamura
IL10 CYCLODEXTRINS IN NANOMEDICINE: RATIONAL DESIGN OF DRUG DELIVERY SYSTEMS, GENE VECTORS AND ANTITOXINS José M. García Fernández, Carmen Ortiz Mellet, Jacques Defaye, Pierre Vierling
IL11 DRUGS AND HIGH-VALUE-ADDED MATERIALS FROM AGRICULTURAL LEFTOVERS Pierre Vogel
IL12 FROM HEMICELLULOSE-DERIVED PENTOSES TO MULTIFUNCTIONAL BUILDING BLOCKS Charles Portella, Richard Plantier-Royon, Ariane Bercier, Sophie Goumain
IL13 CARBOHYDRATES AND RADIATION: TOGETHER THEY WORK M. H. Casimiro, J. P. Leal
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IL14 HOW CARBOHYDRATE RESEARCH SUPPORTS LOCAL AGRO-FOOD PRODUCTION Dulcineia Ferreira
IL15 OLIVE POMACE BIOREFINERY - CONTRIBUTION OF POLYSACCHARIDES Manuel A. Coimbra, Susana M. Cardoso, and José A. Lopes-da-Silva
IL16 GREEN CHEMISTRY FOR SUSTAINABLE DEVELOPMENT AT L’OREAL: SYNTHESIS OF NEW C-GLYCOSIDES OF LARGE INTEREST IN COSMETICS Michel Philippe
IL17 GREEN SUGAR-BASED SURFACTANTS AND MONOMERS FROM MARINE RESOURCES Thierry Benvegnu, Myriam Roussel, Daniel Plusquellec, Jean-François Sassi, Hervé Le Deit, Johann Hendrickx, Yannick Lerat
IL18 CARBOHYDRATES IN PHARMACEUTICAL INDUSTRIES Hans Peter Wessel
IL19 CALIXARENE-BASED GLYCOSIDE CLUSTERS AS POTENTIAL ANTIVIRAL DRUGS Alberto Marra
IL20 BACK TO MY ROOTS: NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF TYPE-2 DIABETES FROM AN ANCIENT HERBAL REMEDY B. Mario Pinto
IL21 BIOPROCESSING OF NATURAL PRODUCTS WITH GLYCOSIDASES Vladimír Kren, Lenka Weignerová, Petr Marhol
IL22 THE USE OF MICROBIAL POLYSACCHARIDES AS VACCINES - POSSIBILITIES, PROBLEMS AND PROSPECTS Stefan Oscarson
IL23 COMPUTATIONALLY-GUIDED GLYCOSCIENCE: TOWARD THE RATIONAL DEVELOPMENT OF CARBOHYDRATE-BASED ANTI-VIRAL THERAPEUTICS Robert J. Woods
IL24 CARBOHYDRATE-ANALYSIS: LIQUID CHROMATOGRAPHY TO SOLVE A CHALLENGE Cees Bruggink, and Detlef Jensen
IL25 FUNCTIONAL FOOD INGREDIENTS FOR GUT HEALTH: EXPLOITATION OF PLANT BIOMASS SOURCES FOR NOVEL INGREDIENTS Robert Rastall
IL26 DIFRUCTOSE DIANHYDRIDE-ENRICHED CARAMELS: PREBIOTIC AND NUTRACEUTICAL PROPERTIES Carmen Ortiz Mellet, Julio Gálvez, Antonio Zarzuelo, Raquel Ruiz, Luis A. Rubio,José M. García Fernandez
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IL27 STUDIES ON THE STRUCTURE OF POLYSACCHARIDES Johannes F.G. Vliegenthart
IL28 COMMERCIALIZATION MODELS OF POTENTIAL GLYCOPRODUCTS Károly Ágoston, Inge Lundt, Joachim Thiem, Arnold Stütz, István Bajza, Lars Kröger, Gyula Dékány
IL29 INFLUENCE OF ANOMERIC CONFIGURATION AND GLYCOSIDIC LINKAGE ON THE SOLUTION CONFORMATIONAL ENTROPY OF OLIGOSACCHARIDES André M. Striegel
IL30 MARINE POLYSACCHARIDES AEROGELS: MATERIALS FOR CATALYSIS AND ADSORPTION Françoise Quignard
IL31 POLYSACCHARIDES TRANSFORMATION, NEW PROCESSES AND TECHNOLOGIES Camélia Stinga, David Guérin, Daniel Samain
IL32 CARBOHYDRATES AS ORGANIC RAW MATERIALS: THE MAJOR CHALLENGES AHEAD Frieder W. Lichtenthaler
OORRAALL CCOOMMMMUUNNIICCAATTIIOONNSS OC1 DESIGN OF AMPHIPHILIC CATALYSTS FOR THE SELECTIVE CONVERSION OF
SUGARS François Jérôme, Nicolas Villandier, Ayman Karam, Joël Barrault, Ronan Pierre and Yves Queneau
OC2 A DUAL PURPOSE IMMOBILIZED BIOCATALYST FOR INULIN AND SUCROSE HYDROLYSIS Pedro Fernandes, Marco P.C. Marques, Stefano Cattorini, Filipe Carvalho, J.M.S. Cabral
OC3 SELF-ASSEMBLIES OF AMPHIPHILIC CYCLODEXTRINS. F. Djedaïni-Pilard, V. Bonnet, M. Roux, B. Perly
OC4 EFFICIENT TELOMERISATION OF BUTADIENE WITH STARCH Julien Mesnager, Anne Lambin, Claude Quettier, Catherine Pinel
OC5 SYNTHESIS OF ACIDIC XYLOOLIGOMER MODEL COMPOUNDS Wilhelm Herok, Beatriz Abad-Romero, Georg Sixta, Clemens Gruber, Herbert Sixta, Paul Kosma
OC6 POLYSACCHARIDES WITH REACTIVE CARBONYLS: CHEMICAL AND PHYSICAL PROPERTIES Bjørn E. Christensen, and Kåre A. Kristiansen
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OC7 SUGARS AND LIGNOSULFONATES RECOVERY FROM SULFITE PULPING OF EUCALYPTUS GLOBULUS BY THE APPLICATION OF MEMBRANE SEPARATION PROCESSES José Augusto Restolho, António Prates, Maria Norberta de Pinho, Maria Diná Afonso
OC8 OXIDATION OF CELLULOSE FROM KRAFT PULP J. A. Figueiredo, Ana Paula Duarte, Suzana Martins, Carla Abrantes, M. Isabel Ismael, Rogério Simões
OC9 THE PROS AND CONS OF THE DEDICATED UPGRADE OF THE HEMICELLULOSIC SUGAR STREAM IN A BIOREFINERY FRAMEWORK Luís C. Duarte, Florbela Carvalheiro, Talita Silva-Fernandes, Francisco M. Gírio
OC10 NOVEL POLYAMIDES FROM DISACCHARIDE-DERIVED DICARBOXYLIC ACIDS Eckehard Cuny, Frieder W. Lichtenthaler
OC11 ISOSORBIDE: A “SUSTAINABLE DIOL” DERIVED FROM SORBITOL FOR THE SYNTHESIS OF NEW AMPHIPHILES Valérie Molinier, Ying Zhu, Morgan Durand, Jean-Marie Aubry
OC12 AN INNOVATIVE AND OPTIMIZED SOL GEL IMMOBILIZATION TECHNIQUE FOR GLYCOSIDES ENZYMATIC HYDROLYSIS Helder Vila-Real, António J. Alfaia, António T. Calado, Maria H.L. Ribeiro
OC13 ENGINEERING TRANSGLUCOSIDASES REGIOSPECIFICITY FOR PROGRAMMED CHEMO-ENZYMATIC SYNTHESIS OF COMPLEX BACTERIAL CARBOHYDRATES Elise Champion, Julien boutet, Karine Descroix, Claire Moulis, Sandrine Morel, Pierre Monsan, Laurence A. Mulard, Magali Remaud-Siméon, Isabelle André
OC14 CARBOHYDRATE – LECTIN INTERACTIONS: PROBING MULTIVALENCY WITH TOPOLOGICALLY DEFINED GLYCOCALIX[4]ARENES Samy Cecioni, Sébastien Vidal, Susan E. Matthews, Anne Imberty, Jean-Pierre Praly
OC15 NOVEL DI-BRANCHED MONOSACCHARIDES AND IMINO SUGARS K. V. Booth, G. W. J. Fleet
OC16 SYNTHETIC APPROACHES TO NOVEL THIOSUGAR SCAFFOLDS CONTAINING α,β-UNSATURATED CARBONYL FUNCTIONS Nuno M. Xavier, Amélia P. Rauter
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PPOOSSTTEERR PPRREESSEENNTTAATTIIOONNSS P1 CONVERSION OF KETOHEXOSES INTO HETEROBICYCLIC GLYCO-HYBRIDS
Ana C. Simão, Arnaud Tatibouët, Amélia P. Rauter, Patrick Rollin
P2 NEW ANTIFUNGAL AND ANTIBACTERIAL COMPOUNDS: 1,3-OXAZOLINE- AND 1,3-OXAZOLIDINE-2-THIONES FilipaV.M. Silva, Jorge Justino, Sandrina Silva, Arnaut Tatibouët, Patrick Rollin, Amélia P. Rauter
P3 SYNTHESIS, ANTIOXIDANT AND ANTICHOLINESTERASE ACTIVITIES AND TOXICITY STUDIES OF OXO-/THIOXOPYRIMIDINE PSEUDO-C-NUCLEOSIDES Rocio Campoy, M. Eduarda M. Araújo, Amélia P. Rauter, Isabel Ismael, J. M. Pinheiro, José A. Figueiredo, Artur M. S. Silva, Jorge Justino, Filipa V. M. Silva, Margarida Goulart
P4 CYTOTOXIC ACTIVITY OF SUGAR-DERIVED �,�-UNSATURATED CARBONYL COMPOUNDS Catarina Sepúlveda, Margarida Meireles, Nuno M. Xavier, Amélia P. Rauter
P5 MASS SPECTROMETRY STUDY OF SUGAR-FUSED BUTENOLIDES Paulo J. A. Madeira, Ana M. T. G. Rosa, Nuno M. Xavier, Amélia P. Rauter, M. Helena Florêncio
P6 PURINE NUCLEOSIDES AS NEW AGENTS FOR THE CONTROL OF ALZHEIMER’S DISEASE Filipa V.M. Silva, Filipa Marcelo, Jorge. Justino, Ana.P. Jacob, Yves. Blériot, Pierre. Sinaÿ, Margarida. Goulart, AméliaP. Rauter
P7 PRACTICAL CONVERSION OF SUGARS INTO HYDROPHILIC N-HETEROCYCLES Eckehard Cuny, Frieder W. Lichtenthaler
P8 BIOACTIVE COMPOUNDS DERIVED FROM FRUCTOSE Ana Catarina Araújo, Amélia P. Rauter, Rossella Zoboli,b Cristina Airoldi, Barbara Costa, Laura Cipolla and Francesco Nicotra
P9 UTILITY OF THE BENZHYDRYL PROTECTING GROUP IN THE SYNTHESIS OF IMINOSUGARS S. F. Jenkinson, R. J. Newell, T. B. Mercer, R. Higham, S. D. Rule, D. Best, A. C. Weymouth-Wilson, S. Petursson, G.W.J. Fleet
P10 SYNTHESIS OF 3-FLUORO OXETANE δ-AMINO ACIDS Susana D. Lucas, Amélia P. Rauter, Hans P. Wessel
P11 NEW METHODOLOGIES FOR THE SYNTHESIS OF FLUORINATED C-GLYCOSIDES Navnath Karche, Benjamin Moreno, Florent Poulain, Eric Leclerc, Jean-Charles Quirion
P12 TRANSFORMATION OF PARTIALLY UNPROTECTED THIOGLYCOSIDES AND n-PENTENYL GLYCOSIDES INTO GLYCOSYL FLUORIDES MEDIATED BY NIS/HF-PYRIDINE Paloma Bernal-Albert, Clara Uriel, Ana M. Gómez, Juan Ventura, J. Cristóbal López
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P13 SYNTHESIS OF gem-DIFLUOROCARBASUGARS AND RELATED PSEUDO-CARBASUGARS João Sardinha, Amélia P. Rauter, Pierre Sinaÿ, Matthieu Sollogoub
P14 1,2 DIFUNCTIONAL SYSTEMS FROM BICYCLIC CARBOHYDRATE LACTONES Y. Queneau, R. Cheaib, N. M. Xavier, A. Listkowski, S. Chambert, A. P. Rauter
P15 SYNTHESIS OF NOVEL ALKYL GLYCOSIDES AS POTENTIAL INHIBITORS/SUBSTRATES FOR MYCOBACTERIAL GLYCOSYLTRANSFERASES M. Poláková, M. Beláňová, K. Mikušová, and L. Petruš
P16 SYNTHESIS OF CYTOTOXIC GLYCOSYLATED DERIVATIVES OF OXYSTEROLS João F. S. Carvalho, M. Manuel Cruz Silva, Sérgio Simões, Sergio Riva,
M. Luísa Sá e Melo
P17 PHENOLS GLYCOSYLATION PROMOTED BY ZEOLITE HY Ana R. Jesus, Miguel M. Santos, Ana P. Carvalho, Amélia P. Rauter, Fernando Ramôa Ribeiro, Michel Guisnet
P18 REDUCTIVE CYCLISATION OF D-GLUCOSE-BASED UNSATURATED SUBSTRATES BY INDIRECT ELECTROCHEMICAL METHODS IN “GREEN” MEDIA C. Durães, A.P. Esteves, M.J. Medeiros and T.A. Dias
P19 C-GLYCOSYLFLAVONOIDS – ARE RARE EARTH METALS CATALYSTS A RELIABLE ALTERNATIVE FOR THEIR SYNTHESIS?
Rui Galhano dos Santos, Nuno Neng, José Nogueira, João Bordado, Amélia P. Rauter
P20 ANTIDIABETIC ACTIVITY AND IDENTIFICATION OF FLAVONOID GLYCOSIDES FROM GENISTA TENERA N-BUTANOL EXTRACT Amélia P. Rauter, Joana Ferreira, Alice Martins, Rui G. Santos, Carlos Borges, Margarida Goulart, Jorge Justino, João P. Noronha, Rui Pinto,Hélder Mota-Filipe, Luísa Roseiro
P21 REGIOSELECTIVE TRANSFORMATION OF CARBOHYDRATES IN AQUEOUS MEDIUM USING ELECTROCHEMICAL METHODS Pier Parpot and A. P. Bettencourt
P22 A NEW CHEMICAL APPLICATION OF LACTOSE: SYNTHESIS OF A �-EPTULOSE Antonino Corsaro, Venerando Pistarà, Maria Assunta Chiacchio, and Giorgio Catelanib
P23 SYNTHESIS OF NEW SUGAR-BASED SURFACTANTS COMBINED CATALYSTS : TOWARDS GREENER CATALYTIC PROCESSES Mathieu Delample, Ayman Karam, Nicolas Villandier, Joël Barrault and François Jérôme
P24 SURFACE-ACTIVE AGENTS FROM RENEWABLE RESOURCES
Tiago Fonseca, Inês Raposeiro, João Bordado
30
P25 CARBOHYDRATES AS CHIRAL INDUCERS IN ASYMMETRIC CATALYSIS: COPPER(II) COMPLEXES OF SUGARS ESTERS & AMIDES DERIVED FROM 2,2'-BIPYRIDINE FOR ENANTIOSELECTIVE ELECTROPHILIC FLUORINATION Aurélie Assalit, Thierry Billard, Bernard Langlois, Yves Queneau, Stéphane Chambert, Diane Coe
P26 NOVEL SUPRAMOLECULAR DIMERS OF CYCLODEXTRIN DERIVATIVES F. Hamon, B. Violeau, F. Turpin, E.M. Belgsir, Y. Cenatiempo, F. Djedaïni-Pilard, C. Len
P27 CHEMICAL MODIFICATION OF A BACTERIAL POLYSACCHARIDE FOLLOWING HOMOGENEOUS OR HETEROGENEOUS PROCEDURES Rudy Covis, Catherine Ladavière, Emmanuelle Marie, Alain Durand
P28 CHEMICAL AND ENZYMATICAL MODIFICATIONS OF SUGAR DERIVED FROM LIGNOCELLULOSE Gaëtan Richard, Pascal Laurent, Katherine Nott, Aurore Richel, Murielle Helleputte, Jean-Paul Wathelet, Michel Paquot
P29 OXIDATION OF POLYSACCHARIDES: FROM STOICHIOMETRIC PROCESSES TOWARD CATALYTIC CLEAN ROUTES Svetlana L. Kachkarova, Pierre Gallezot and Alexander B. Sorokin
P30 ANALYSIS OF DFAS IN PREBIOTIC CARAMELS: A COMBINATION OF HPAEC-PAD, MS AND STEREOSELECTIVE SYNTHESIS Elena Suárez-Pereira, Carmen Ortiz Mellet, Antoine Fournez, David Lesur, Serge Pilard, and José M. García Fernandez
P31 SYNTHESIS OF ALKYLATED AND THIOALKYLATED MALTODEXTRINE DERIVATIVES AND EVALUATION OF THEIR ANTIMICROBIAL AND ANTI-INFLAMMATORY PROPERTIES Vincent Moreau, Nicolas Thiebault, David Lesur, Paul Godé, Patrice André, Jean-Christophe Archambault, F. Djedaïni-Pilard
P32 DERMO-COSMETIC PERFORMANCES OF NEW FORMULATIONS CONTAINING HALURONATE BUTYRIC AND FORMIC ESTERS M. Bosco, L. Cocchi, M. Fabbian, R. Gianni, F. Picotti, L. Stucchi, A. Trevisan
P33 NEW HYALURONIC ACID DERIVATIVES AND THEIR APPLICATIONS M. Bosco, M. Fabbian, R. Gianni, F. Picotti, L. Stucchi, A. Trevisan
P34 REACTIVITY OF SUCROSE-LIKE TRISACCHARIDES: RAFFINOSE AND MELEZITOSE Céline Besset,Stéphane Chambert, Alain Doutheau, Bernard Fenet, Jérôme Guilbot, Hervé Rolland, Sébastien Kerverdo, Yves Queneau
P35 THE USE OF ISOSORBIDE DERIVATIVES AS BIO-SOURCED ALTERNATIVES TO PETROLEUM-DERIVED PRODUCTS FOR DETERGENT APPLICATIONS Morgan Durand, Ying Zhu, Valérie Molinier and Jean-Marie Aubry
P36 MULTI-LACTOSIDES BASED ON CARBOHYDRATE SCAFFOLDS FOR STUDYING SUGAR-LECTIN INTERATIONS S.G. Gouin, J. Kovensky
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P37 GENE DELIVERY VEHICLES BASED ON AMPHIPHILIC β-CYCLODEXTRIN “CLICK CLUSTERS” Alejandro Méndez-Ardoy, Marta Gómez-García, Carmen Ortiz Mellet, M. Dolores Girón-González, Natalia Sevillano-Tripero, Rafael Salto-González, Francisco Santoyo-González, and José M. García Fernández
P38 GLUTATHIONE RESPONSIVE POLYURETHANES AS POTENTIAL MATERIALS FOR BIOMEDICAL APPLICATIONS M. Violante de Paz, Francisca Zamora, Juan A. Galbis
P39
NEW AMPHIPHILIC GLYCOPOLYMERS BASED ON A POLYCAPROLACTONE-MALEIC ANHYDRIDE BACKBONE. CHARACTERIZATION BY 15N NMR AND USE FOR THE COLLOIDAL STABILIZATION OF NANOPARTICLES Otman Otman, Paul Boullanger, Dominique Lafont, and Thierry Hamaide
P40 CHEMICAL MODIFICATION OF URONIC ACIDS AND OLIGOURONIDES UNDER MICROWAVE IRRADIATION IN SOLVENT FREE CONDITIONS Stéphanie Rat, José Kovensky, Philippe Michaud, Anne Wadouachi
P41 AQUEOUS-PHASE EXTRACTION OF GLUCURONOXYLANS FROM CHESTNUT WOOD: NEW STRATEGY FOR LIGNIN OXIDATION USING PORPHYRIN OR PHTHALOCYANINE IN H2O2 SOLUTIONS Aline Barbat, Vincent Gloaguen and Pierre Krausz
P42 HYDROLYSIS OF SUCROSE OVER SULFONATED POLY(VINYL ALCOHOL) D.S. Pito, I.M. Fonseca, A.M. Ramos, J. Vital, J.E. Castanheiro
P43 DEHYDRATION OF D-XYLOSE INTO FURFURAL BY SOLID ACIDS DERIVED FROM A LAYERED ZEOLITE Sérgio Lima, Martyn Pillinger, Anabela A. Valente
P44 CATALYTIC DEHYDRATION OF D-XYLOSE TO FURFURAL Anabela A. Valente, Ana S. Dias, Sérgio Lima, Martyn Pillinger
P45 SYNTHESIS OF LEVULINIC ACID : A COMPARAISON BETWEEN PRESSURIZED BATCH AND REACTIVE EXTRUSION PROCESS
Pierre Ferchaud, Hélène Ducatel, Camille Viot, Philippe De Braeckelaer, Anne Wagner, Maurice Essers, Denis Postel
P46 CARBOHYDRATES EXTRACTION FROM AQUEOUS SOLUTIONS USING IONIC LIQUIDS Andreia A. Rosatella, Luís C. Branco, Carlos A.M. Afonso
P47 INFLUENCE OF ISOLATION METHODS ON PROPERTIES OF CHESTNUT STARCH Paula M. Correia, Maria L. Beirão-da-Costa
P48 ALGINATE AEROGELS AS ADSORBENTS OF POLAR MOLECULES FROM LIQUID HYDROCARBONS Francesco Di Renzo, Rosalia Rodriguez Escudero, Mike Robitzer, and Françoise Quignard
P49 WINE ADITIVATION WITH CORK Luis Gil, Carlos Pereira
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P50 CARBOHYDRATE-BASED LIQUID CRYSTALS: SYNTHESIS AND THERMOTROPIC BEHAVIOUR OF NEW MULTIFUNCTIONAL SYSTEMS CONSTRUCTED FROM CMGL SYNTHONS Fahima Ali Rachedi, Stéphane Chambert, Stephen J. Cowling, John W. Goodby, and Yves Queneau
P51 SYNTHESIS AND PROPERTIES OF NEW CARBOHYDRATE BASED FLUORESCENT PROBES FOR NON-LINEAR OPTIC MEMBRANE IMAGING S. Chambert, R. Cheaib, C. Barsu, Y. Bretonnière, O. Maury, A. Girard-Ergot, L. Blum, C. Andraud and Y. Queneau
P52 SYNTHESIS AND RAFT POLYMERIZATION OF NEW ACRYLAMIDE BASED GLYCOMONOMERS Ouaiss Abdel Kader, Julien Bernard, Stéphane Chambert, Sylvie Moebs,Etienne Fleury, Yves Queneau
P53 PHOTOSENSITIZERS GRAFTED ON CELLULOSE FABRICS: NEW PHOTOBACTERICIDAL MATERIALS Cyril Ringot, Vincent Sol, Robert Granet, Pierre Krausz
P54 ENZYMATIC POLYESTERIFICATION REACTIONS OF αααα-HYDROXY DICARBOXYLIC ACIDS
M. Gracia García-Martín, E. Benito and Juan A. Galbis
P55 NEW XYLO-OLIGOSACCHARIDES PRODUCED FROM CORN COBS BY ENZYMATIC HYDROLYSIS Susana Marques, Andreia Dias, Francisco M. Gírio, and Patrícia Moura
P56 XYLO-OLIGOSACCHARIDES FROM LIGNOCELLULOSIC WASTES: TOWARDS A SYMBIOTIC PREPARATION WITH Bifidobacterium adolescentis Patrícia Moura, Patrícia Gullón, Juan Carlos Parajó, Francisco M. Gírio
P57 ANALYSIS OF OLIGOSACCHARIDES BY CAPILLARY-SCALE HIGH-PERFORMANCE ANION-EXCHANGE CHROMATOGRAPHY WITH PULSED AMPEROMETRIC DETECTION (CHPAEC-PAD) AND ON-LINE ELECTROSPRAY-IONIZATION ION-TRAP MASS SPECTROMETRY (CHPAEC-ITMS). C Bruggink, CAM Koeleman, V Barreto, Y Lui, C Pohl, A Ingendoh, M Wuhrer,CH Hokke, AM Deelder
P58 LOW MOLECULAR WEIGHT OLIGOSACCHARIDES: STUDIES ON MOLECULAR MOBILITY OF AMORPHOUS PHASE AND ON THE ENERGETICS OF CRYSTALLINE FORM Susana S. Pinto, Hermínio P. Diogo, Joaquim J. Moura Ramos
P59 CARBOHYDRATES FROM BIOMASS AS A SOURCE OF BIOETHANOL N. Gil, F.C. Domingues, M.E. Amaral, A.P. Duarte
P60 SUGARCANE MOLASSES AS A LOW-COST STRATEGY TO IMPROVE STABILITY OF ANAEROBIC TREATMENT OF A PULP MILL EFFLUENT Flávio Silva, Marta Barbosa, Helena Nadais, António Prates, Luís Arroja, Isabel Capela
P61 TREATMENT OPTIMIZATION OF RAW CANE SUGAR REFINING EFFLUENT S. M. Nunes, H. M. Pinheiro, M.T. Duarte, J. C. Bordado, V. M. Vicente
33
P62 GAMMA IRRADIATED CHITOSAN/pHEMA FILMS TO BE USED AS SUPPORT IN DRUG RELEASE SYSTEMS M. H. Casimiro, J. P. Leal
P63 SURFACTANT-FREE AB INITIO EMULSION POLYMERIZATION OF VINYL ACETATE USING A DEXTRAN-BASED XANTHATE AGENT SYNTHESIZED BY CLICK CHEMISTRY Julien Bernard, Maud Save, Benoit Arathoon, Bernadette Charleux
35
AABBSSTTRRAACCTTSS
Invited Lectures IL1 – IL32
Oral Communications OC1 – OC16
Poster Presentations P1 – P63
37
IL1
BACK TO THE BIO-FUTURE
Serge Pérez
Centre de Recherche sur les Macromolécules Végétales, CNRS, Université Joseph Fourier, Grenoble, France. [email protected]
Less than 300 years of modern industry and modern consumerism will have exhausted fossil resources that have accumulated over 150-200 millions years. Up to the beginning of the 20th century renewable agricultural carbohydrates constituted the raw materials for fuel, chemical and material production. They were gradually replaced by petroleum based derivatives. The depletion of petroleum resources, along with the current concerns about the warming of the planet that can be attributed to human activities, make it urgent to shift dependence away from fossils resources to renewable biomass resources. Sustainable alternatives should be developed commercially in the very near future, both in terms of energy production and commodity products. As for the future energy generation only a multi-faceted approach is likely to provide a viable solution; it will include nuclear, hydroelectricity, solar, hydrogen, wind and biofuel… At the present time, biofuel may be expected to cover a small percentage of the total power that could be generated. The dual goal of producing bio-power and biomaterials, while enhancing the management of greenhouse emissions should be pursued. To this end, the concept of bio-refinery has been proposed, which parallels the petroleum refinery, in the imbalance between transportation fuels and chemical needs. The bio-refinery operates on an abundant renewable raw materials (ligno-cellulosic, polysaccharides,….) which are fractionated, through a series of processes, and further converted into commodity chemical molecules and transportation fuels. In order for the bio-refinery to be effective, significant and concomitant advances in genetics, “green” and “white” biotechnologies, process chemistry and engineering should be pursued. This would lead, among other, to significant changes in agronomical practices with innovation in plant resources. The imbalance between food / non food utilization of these agro-resources should be a major and constant concern. The integration of biosciences with engineering principles is leading to the development of biochemical engineering. The contribution of plant biologists, carbohydrate chemists and process engineers to the implementation of the bio-refinery is likely to be essential. The parallel between petroleum refinery and bio-refinery provides reasonable foundation for the economical realism of this concept. It is nevertheless obvious that other concepts such as those embedded into the “Green Chemistry” principles will be incorporated within the new manufacturing paradigm. The mere fractionation of abundant biosynthesized raw materials is far from having the adhesion of all the scientific community; alternative concepts to the bio-refinery concept are also emerging. It is advocated that the depletion of petroleum resources is unavoidable within the next half century or more, but that about 5% of the total petroleum output from a conventional refinery goes to chemical products. This means that the current resources are more than adequate to fill the chemical industry for many more years. Bio-processing will dominate over chemical processing only by improving its capital, operating cost requirement, and bringing added-values and innovation. This can be performed based on the “intelligent” use of the unique bio-molecular and bio-macromolecular architectures that are derived from biosynthetic pathways and that are not attainable throughout thermodynamically driven processes. Our most recent knowledge about the different levels of structural organizations are providing rationale ways of conducting chemical modifications while keeping the biodegradable and recyclable features of the starting raw material. Exploring these new frontiers, far from the concept of “replacement”, is likely to stimulate the whole carbohydrate community that can incorporate sophisticated synthetic methodology, glycobiology, plant polysaccharides and plant sciences to help shifting society’s dependence away from petroleum to renewable biomass resources.
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IL2
BIOHUB® PROGRAM FOR THE DEVELOPMENT OF NEW CEREAL-BASED BIO-REFINERIES
Patrick Fuertes
Roquette Frères, F-62080 Lestrem CEDEX, [email protected] The use of renewable raw materials of vegetal origin constitutes one of the most promising areas of development for sustainable chemicals.
The R&D programs launched in numerous countries for the production of biofuels is currently coming to fruition with significant production of bio-diesel and bio-ethanol, and constitutes one of the first major steps towards the exploitation of renewable raw materials.
Conversely, the chemicals industry still remains highly oriented towards the development of processes based on raw materials of fossil origin. The rarefaction of these resources and the increase in crude prices are factors that will lead to a progressive change in the chemicals industry towards the introduction of new biorefineries.
Today’s starch-production plant is a good example of a bio-refinery, which uses enzymatic and/or chemical conversion to produce a broad range of products, including starch, glucose, sorbitol and derivatives such as isosorbide.
Since the mastery of catalytic systems and processes allow us to obtain very pure products in a competitive manner, and enable the development of biotechnologies, they promise to significantly broaden the range of starch-based products, in areas of application traditionally reserved to the world of petrochemicals.
To this end, ROQUETTE and its scientific and industrial partners have presented in April 2006 a program to the Agency of Industrial Innovation (AII) : the BioHub® program. The BioHub® program was accepted by the AII in April 2006 and by the European Commission in December 2006.
The program is led by ROQUETTE in partnership with seven other industrial entities, including the chemicals companies ARKEMA (France), DSM (Pays-Bas), SOLVAY (Belgium) and COGNIS (Germany), the roadway-design company EUROVIA (VINCI Group), SIDEL, a company specialized in polymer-bottling systems, and TERGAL INDUSTRIES, a producer of PET.
The partnership also includes METABOLIC EXPLORER, a young start-up based in Clermont-Ferrand, which specializes in the industrial application of biotechnology techniques.
The CNRS, meanwhile, is also well represented in the BioHub® program, with teams from the National Institute of Applied Sciences (INSA) from Lyons and Rouen and from the Institute of Molecules and Condensed Materials of Lille (IMMCL).
The goal of the BioHub® program is to develop new channels of production for chemical products based on renewable agricultural raw materials such as cereals.
Among the new products arising from this research program are biopolymers, biosolvents, bioplastics, biocomplexants, and active and intermediary ingredients for synthesis.
With the BioHub® program, ROQUETTE expects to play a leading role in industrial innovation in the service of chemistry for sustainable development.
39
IL3
NEW BIODEGRADABLE AND FUNCTIONAL POLYMERS FROM EASILY AVAILABLE SUGARS
Juan A. Galbis
Department of Organic and Pharmaceutical Chemistry, University of Seville, 41071 Seville (Spain).
The environmental impact produced by the massive use of the plastic materials mostly synthesized from monomers obtained in the petrochemical industry from the fossil resources and the everyday more restricted access to these resources have drawn attention to natural renewing sources for the chemical synthesis of polymers. The polymers based on naturally occurring products are promising, new materials, with novel technical possibilities and improved properties, such as biocompatibility and biodegradability.1 Among the different natural sources, carbohydrates stand out as highly convenient raw materials because they are inexpensive, readily available, and provide great stereochemical diversity.2
Aliphatic polyamides (nylons®), aromatic polyesters (PET and PBT), polycarbonates and polyurethanes are widely recognized polymers because of their excellent technical properties. However, the low hydrophilicity, resistance to hydrolysis, and lack of biodegradability displayed by these polymers are serious shortcomings that limit their applications and make their recovery by chemical recycling difficult. In earlier papers published by our group3-6 we described the preparation and characterization of carbohydrate-based AB-type and AABB-type polymers having an enhanced hydrophilicity and biodegradability.
In this lecture, I will present the last results obtained in our group on the preparation of new carbohydrate-based polymers obtained by polycondensation and polyaddition reactions, their structures and properties.
1 Vert, M., Feijen, J., Albertsson, A., Scott, G., Chiellini, E., Eds. Biodegradable Polymers and Plastics, The Royal Society of Chemistry, Cambridge, UK., 1992.
2 Galbis, J. A., García-Martín, M. G. Sugars as Monomers. In: A. Gandini, M. N. Belgacem, Eds. Monomers, Oligomers, Polymers and Composites from Renewable Resources. Elsevier, Amsterdam, 2008. (Chapter 5). pp. 89-114.
3 Alla, A., Hakkou, K., Zamora, F., Martínez de Ilarduya, A., Galbis, J. A., Muñoz-Guerra, S. Macromolecules 2006, 39, 1410-1416.
4 De Paz, M. V., Marín, R., Zamora, F., Hakkou, K., Alla, A., Galbis, J. A., Muñoz-Guerra, S. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 4109-4117.
5 De Paz, M. V., Aznar, J. A., Galbis, J. A. J. Carbohydr. Chem. 2008, 27, 120-140. 6 Zamora, F., Hakkou, K., Alla, A., Marín, R., De Paz, M. V., Martínez de Ilarduya, A., Muñoz-Guerra,
S., Galbis, J. A. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 5167-5179.
40
IL4
CARBOHYDRATES FOR ETHANOL AND DISTILLED BEVERAGES
Henrique Amorim
Fermentec Av. Antonia Pizzinato Sturion 1155 Jd. Petrópolis
Cep: 13420640 Piracicaba SP, Brasil. [email protected] Carbohydrates had been used for ethanol production for thousands of years. In the beginning a natural fermentation to produce alcoholic beverages has been mentioned in the literature. Fermented beverages it is known to be drank for more than 10.000 years.
The presentation will summarize the most important carbohydrates used today in an industrial scale to produce ethanol as fuel and industrial grade ethanol, and also some important distillate beverages like cachaça (Brazil), tequila (México) and run (Caribe).
Carbohydrates for fuel and industrial alcohol are extracted from sugar cane (sucrose, glucose and fructose) and used up directly by the yeast convert into ethanol. The grains (corn, wheat, sorghum, etc.) have the starch as the substrate for the ethanol production. However, the starch has to be hydrolyzed by two enzymes, alfa-amilase and glucoamilase to be transformed by the yeast to ethanol.
Cachaça and run have the same carbohydrates as substrate (sucrose, glucose and fructose), although cachaça uses the cane juice and run the molasses (residual sugar from a sugar factory). Both fermented mash are distilled to produce the beverage.
Tequila uses a polysaccharide like inulin (fructosan) which is hydrolyzed (given fructose) by heating the agave plant to be used by the yeast to produce ethanol and them, distilled to produce the tequila beverage.
41
IL5
ADVANTAGES IN PROCESSING WHITE SUGAR WHEN SUGAR FACTORIES ARE ASSOCIATED WITH AN ETHANOL PLANT
Luis S.- M. Bento
Sucropedia
www.sucropedia.com
Cane sugar industry utilizes sugar cane to produce raw sugar in mills. Raw sugar is then refined to white sugar, in separate unities. Some sugar mills produce ethanol from molasses or from juice in attached ethanol plants, jointly with white sugar. In this case, the sugar processing can be changed in order to have a more efficient, more economical and less pollutant process. In this paper are presented the changes that the ethanol production allows to the sugar processing. Some of these changes, as separating the low purity juices for ethanol production, are already applied. However other changes, as utilization of ethanol as a regeneration chemical in decolourizers systems are not applied nowadays. These changes will open the possibility to produce white sugar directly in cane mill with a much more economical process. Some of the changes presented here can also be applied in beet sugar industry.
42
IL6
SUCROSE – A PROSPERING AND SUSTAINABLE ORGANIC RAW MATERIAL
Matthias Moser
Südzucker AG Mannheim/Ochsenfurt, Central Research Development and Services, Wormser Straße 11, 67283 Obrigheim, Germany.
E-mail: [email protected]
Sucrose is produced on the industrial scale from sugar beet or sugar cane with a present annual production of 161 Mio metric tons (2006/07). It is the most available carbohydrate and until now mainly used for nutrition purposes, bioethanol production (Brazil) and in the fermentation industry. Only to a smaller extend sucrose has been utilized as feedstock for organic chemicals. And this, though many attempts have already disclosed the valorisation of sucrose for this purpose.1,2 By the following three basic reaction pathways sucrose could be converted into valuable chemical compounds.
1.) By degradation of the sucrose skeleton: The announced bio-ethylene production via bio-ethanol in Brazil appears to be one of the most promising approaches which open the door for the whole ethylene derived C2-chemistry. Also 5-(hydroxymethyl)furfural (HMF) and levulinic acid are regarded as valuable sugar-derived intermediates for chemical products, for the time being regrettably not yet able to compete in price with petrochemical derived products. Catalytic hydrogenation of sucrose under elevated temperature and pressure opens access to valuable polyhydric compounds, like 1,2-propylene glycol, useful in many cosmetic, pharmaceutical and technical applications.
2.) By reactions of sucrose under preservation of the sucrose scaffold: These reactions fortunately lead to several products of interest for food and non-food application. Among these compounds are sucrose esters, polyurethanes and also the well known high intense sweetener sucralose.
3.) By modifications maintaining carbohydrate structure: Technical interesting substances could be achieved from sucrose by enzymatic cleavage and/or rearrangement of the sucrose building blocks D-glucose and D-fructose, thereby giving access to products like isomaltulose (commercially available as palatinose™) and isomalt or polymeric compounds like oligofructose, inulin and levan or neo-amylose and dextran.
Many valuable contributions demonstrate impressively the utilisation of sucrose as feedstock for basic chemical compounds. The hesitant implementation in industry appears clearly cost driven and may change due to the estimated medium-term shortage of petrochemical feedstocks. As a renewable organic bulk chemical sucrose seems to be predestined as potential “player” as a feedstock for the chemical industry.
1 Y. Queneau, S. Jarosz, B. Lewandowski, J. Fitremann, Adv. Carb. Chem. Biochem., 2007, 61, 217. 2 F. W. Lichtenthaler in Biorefineries – Industrial Processes and Products , Eds. B. Kamm, P. R.
Gruber, M. Kamm, Wiley-VCH, Weinheim, 2006, 2, S. 3.
43
IL7
WHAT CAN BE DONE FROM SUCROSE? TOWARDS MACROCYCLIC RECEPTORS WITH SUCROSE SCAFFOLD
Slawomir Jarosz
Institute of Organic Chemistry, Polish Academy of Sciences Kasprzaka 44/52, 01-224 Warsaw Poland, [email protected]
Sucrose, a cheap raw material, is available in more than 140 million tons per year; most of it is consumed on the food market. This chemical is very demanding to work with, because of its very poor solubility in most organic solvents, the presence of eight hydroxyl groups which are difficult to differentiate, and high sensitivity of the glycosidic bond in acidic media. However, this disaccharide is also a subject of interest as a starting material for the preparation of fine chemicals, as well as bio-degradable polymers or surfactants.1 We have elaborated a convenient route to hexa-O-benzylsucrose (1) which served as starting material for the preparation of macrocyclic receptors of type 2. One of them (3) showed remarkable high enantioselectivity towards chiral amines.
Approach to receptors with higher symmetry (such as e.g. 4) will be also presented.2
1 Recent review: Queneau, Y., Jarosz, S., Lewandowski, B., Fitremann, J. Adv. Carbohydr. Chem. Biochem., 2007, 61, 217-300.
2 Jarosz, S., Lewandowski, B., Synthesis 2008, 913-916; Jarosz, S., Lewandowski, B., Carbohydr. Res. 2008, 343, 965-969.
44
IL8
GLYCONANOMATERIALS AND APPLICATIONS
Soledad Penadés
Laboratory of GlycoNanotechnology, CICbiomaGUNE and Networking Centre on Bioengineering, Biomaterials, and Nanomedicine, CIBER-BBN
Parque Tecnológico de San Sebastian, Paseo de Miramon 182, 20009 San Sebastian, Spain Email address ([email protected])
To study and intervene in carbohydrate interactions our laboratory has developed an integrated strategy (Glyconanotechnology) to produce 2D- and 3D-gold surfaces functionalized with self-assembled monolayers (SAMs) of sugars. By combining these glyconanomaterials with novel analytic surface techniques (AFM, TEM, SPR) we have demonstrated and evaluated Ca2+-mediated carbohydrate-carbohydrate interactions involved in a diversity of biological processes. The 2D-surfaces have been used in the study of chemical forces between carbohydrate-carbohydrate interactions by AFM. The 3D-gold surfaces (glyconanoparticles,GNPs) coated with biological significant carbohydrates (antigens) and with differing density have been prepared to study biological mechanisms and to intervene in cell adhesion processes. The methodology includes the preparation of multifunctional GNPs incorporating carbohydrates and other molecules such as fluorescent molecules, biotin, peptides, proteins, antibodies or DNA. The manipulation of the metallic cluster to obtain luminescent glyco-quantum dots (semiconductors) and magnetic nanoparticles for application in cellular labelling and imaging is comprised within the potential of this novel technology. Furthermore, the introduction of additional ligands can be used to guide the assembly of the nanoclusters creating a wealth of different nanostructured materials. The glyconanomaterials presented here are excellent probes for understanding biomolecular interactions and potential instruments to solve biomedical problems. In this lecture, the Glyconanotechnology strategy will be presented and some of their applications will be highlighted.
45
IL9
LINEAR AND CYCLIC AMYLOSES: BEYOND NATURAL
Shinichi Kitamura
Graduate School of Life and Environmental Sciences, Osaka Prefecture University,
Sakai, Osaka 599-8531, Japan [email protected] This presentation outlines the progress of recent studies on synthetic linear and cyclic amyloses. Unlike linear amylose, which has a long history1, cyclic amylose (large-ring cyclodextrins, referred to as cycloamylose in this paper) was discovered recently as a result of the action of recombinant potato D-enzyme (4-α- glucanotransferase, EC 2.4.1.25) on linear amylase2. The degree of polymerization (dp) of cycloamylose isolated from reaction mixtures has been found to range from 17 to several hundred. Available information on the conformation and molecular characteristics of cycloamylose are limited3.
Linear amylose has been widely studied, largely because of its interesting solution properties, which include complex formation with iodine, butanol, and other organic reagents, as well as a tendency for molecular association (retrogradation). Synthetic linear amylose can be produced using either glucan phosphorylase or coupling of sucrose phosphorylase and glucan phosphorylase4. The chain length can be controlled by changing the reaction conditions. These amyloses are strictly linear molecules and have a narrow molecular-weight distribution. While aqueous solutions of linear amylose are very unstable over a range of from dp 20 to 200, shorter and longer molecules are much more soluble. Linear synthetic amyloses with dp > 4000 can be soluble in water and stable for a long time. For example, a 1% aqueous solution of amylase (dp 5200) is stable for more than one month at room temperature.
Members of this group of ring polymers (cycloamylose) are stable in water even over a range of from dp 20 to 100. SAXS measurements and simulations demonstrate that a cycloamylose in dilute solution can be modeled as a circularized single helix and that the scattering functions that are computed for pseudo-cyclic amylose chains when using the Monte Carlo method agree well with the experimental curves for cycloamylose. Cycloamylose has the potential to function as a host molecule for a variety of organic reagents, and with iodine, in a manner that is different from linear amylose and different from the more common cyclodextrins (α-,β-, γ-CDs). It is likely that cycloamylose has a cavity geometry that differs from those of linear amylose and these CDs. We studied the complex formations of cycloamylose with iodine and surfactants in aqueous solution by isothermal titration calorimetry, and compared these results with those obtained for linear amylose.
These synthetic amylases are now commercially available and many applications are now in development. I will show some examples that display these characteristic physical properties.
1 S. Kitamura, in Polymeric Materials Encyclopedia, Vol.10, p.7915, J.C. Salamone Ed. (CRC Press,
Florida, 1996). 2 T. Takaha, M.Yanase, H. Takata, S. Okada, S.M. Smith, J. Biol. Chem., 271, 2902 (1996). 3 S. Kitamura, in Cyclic Polymers, Chapter 4, p125 J.A.Semlyen Ed. (Kluwer Academic Publishers,
Dordrecht, 2000) . 4 H. Waldmann, D. Gygax, M. D. Bednarski, W. R. Shangraw, G. M. Whitesides, Carbohydrate
Research, 157, c4-c7, (1986).
46
IL10
CYCLODEXTRINS IN NANOMEDICINE: RATIONAL DESIGN OF DRUG DELIVERY SYSTEMS, GENE VECTORS AND ANTITOXINS
José M. Garcia-Fernández,a* Carmen Ortiz-Mellet,b Jacques Defaye,c and Pierre Vierlingd
(a) Instituto de Investigaciones Químicas, CSIC – Univ. Sevilla, E-41092 Sevilla, Spain,
* [email protected] (b) Dpto. de Química Orgánica, Facultad de Química, Univ. Sevilla, E-41012 Sevilla, Spain
(c) Dept. de Pharmacochimie Moleculaire, Institut de Chimie Moleculaire de Grenoble (CNRS – Univ. Grenoble, UMR 5063, FR2607), F-38041 Grenoble, France
(d) LCMBA UMR 6001 CNRS – Univ. Nice Sophia Antipolis, F-06100 Nice, France
Cyclomaltooligosaccharides (cyclodextrins, CDs) are a class of industrially available supramolecular nanobiomaterials now readily adaptable to further manipulation in order to modulate their topology and recognition features.1 Regioselective functionalization of their hydroxyl groups has already been exploited in the design of glycodendritic site-specific drug delivery systems2 and glycocalix mimics (third-generation CDs).3 Fourth-generation CDs, involving the capability to self-assemble and interact with larger structures, are now developed. By taking advantage of the tubular structure and topical anisotropy of the molecule, different functional elements with a dedicated spatial orientation can be installed to favour aggregation, encapsulation or binding phenomena. Three examples that illustrate this concept will be presented, namely the design of a tailor-made carrier for the anticancer drug Taxotère®,2 CD-based artificial viruses for gene delivery (see Figure)4,5 and nanometric blockers against the pore-forming protein associated to anthrax toxin. 1 García Fernández, J. M.; Ortiz Mellet, C.; Defaye, J. J. Incl. Phenom. Macrocycl. Chem. 2006, 56,
149-159. 2 Benito, J. M.; Gómez-García, M.; Ortiz Mellet, C.; Baussanne, I.; Defaye, J.; García Fernández, J. M.
J. Am. Chem. Soc. 2004, 126, 10355-10263. 3 Gómez-García, M.; Benito, J. M.; Rodríguez-Lucena, D.; Yu, J.-X.; Chmurski, K.; Ortiz Mellet, C.;
Gutiérrez Gallego, R.; Maestre, A.; Defaye, J.; García Fernández, J. M. J. Am. Chem. Soc. 2005 127, 7970-7971.
4 Díaz-Moscoso, A.; Balbuena, P.; Gómez-García, M.; Ortiz Mellet, C.; Benito, J. M.; Le Gourriérec, L.; Di Giorgio, C.; Vierling, P.; Mazzaglia, A.; Micalli, N; Defaye, J; García Fernández, J. M. Chem. Commun. 2008, 2001-2004.
5 Ortega-Caballero, F.; Ortiz Mellet, C.; Le Gourriérec, L.; Di Giorgio, C.; Vierling, P.; Defaye, J.; García Fernández, J. M. Org. Lett. 2008, in press.
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47
IL11
DRUGS AND HIGH-VALUE-ADDED MATERIALS FROM AGRICULTURAL LEFTOVERS
Pierre Vogel
Laboratory of glycochemistry and asymmetric synthesis (LGSA)
Swiss Federal Institute of Technology in Lausanne (EPFL) Batochime, CH 1015 Lausanne, Switzerland
[email protected] With the future exhaust of petroleum and coal that represent our raw materials for material sciences, crop protecting agents and drugs, our civilization is confronted with the urgent need to find new sources of carbon containing raw materials. Vegetable biomass, generated from CO2, H2O and using sunlight as the energy source producing O2 as a sub-product, is the best alternative to oil, gas and coal. Plants have to be used to feed men. To divert them into fuel and fine chemical production cannot be done at this moment, unless new plants are found that can have a better photochemical yield for the conversion of CO2 into carbohydrates and other compounds, and would not require huge amount of water. Thus as long as one cannot grow biomass in the desert, only the leftovers (mainly straw) can be used as a sources of fuel and fine chemicals.1 For many years our laboratory has developed synthetic methodology permitting to convert furans into high value added chemicals such as drugs. Furans (furan, furfural, (2-furan)methanol, 5-hydroxymethylfurfural, 2,5-dimethylfuran) are inexpensive, non-toxic compounds obtained by acidic treatment of straw (gold from garbage).2 These products will substitute petroleum-derived chemicals that are now necessary for our civilization (energy, crop protection, health, materials, telecommunication, etc.). This presentation gives applications of our furan chemistry. We have demonstrated that furan, and its readily available derivatives, can be used to construct highly sophisticated compounds of biological interest such as anti-tumoral anthracyclines (combinatorial synthesis of polycyclic systems by tandem Diels-Alder additions3), sugar-like drugs (through the “naked sugar” methodology4) and polyketide antibiotics (starting from furan and (2-furan)methanol5,6). Enantiomerically pure compounds have been obtained from readily available leftovers such as tartaric acids (from wine) or from camphor derived from trees. The chemistry we have developed contributes toward sustainable development. 1 Corma, A.; Iborra, S.; Velty, A. Chem. Rev. 2007, 107, 2411-2502. 2 Chheda, J. N.; Huber, G. W.; Dumesic, J. A. Angew. Chem. Int. Ed. 2007, 46, 7164-7183. 3 Vogel. P. Anthracycline Chemistry and Biology I, Topics in Current Chemistry 282, Springer, 2008, p.
187-214. 4 Vogel, P. Curr. Org. Chem. 2000, 4, 455-480; Organic Chemistry of Sugars, Levy, D. E. ed., CRC
Press, Boca Raton, FL. 2006, 629-725. 5 Gerber-Lemaire, S.; Vogel, P. Eur. J. Org. Chem. 2003, 2959-2963. 6 Favre, S.; Gerber-Lemaire, S.; Vogel, P. Org. Lett. 2007, 9, 5107-5110.
48
IL12
FROM HEMICELLULOSE-DERIVED PENTOSES TO MULTIFUNCTIONAL BUILDING BLOCKS
Charles Portella*, Richard Plantier-Royon, Ariane Bercier, Sophie Goumain
Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR
6229, UFR Sciences Exactes et Naturelles, BP 1039, 51687 Reims Cedex 2, France [email protected]
Hemicellulose is an abundant component (~25% of dry matter) of wheat industry by-products such as bran and straw. D-Xylose and L-arabinose, the main components of wheat hemicellulose, are two epimeric pentoses the stucture of which differs at the C-4 configuration. This feature is responsible for several significant differences in their physico-chemical properties. That is not problematic for applications towards products where a strict molecular structure is not mandatory as in surfactants field, where the starting material is a mixture of sugars.1 On the other hand any attempt to consider D-xylose or L-arabinose as a source for organic intermediates for fine chemistry applications should use pure starting material, except if we were able to transform both epimeric sugar into a common intermediate.
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We will present several approaches to show the feasibility of this co-transformation concept3 and some preliminary results on further transformation of the enal. 1 Bertho, J.-N.; Mathaly, P.; Dubois, V.; De, Baynast De Septfontaines R. Eur. Pat. EP 699472
(CAN 124:292924), 1996. 2 a) Bernet, B.; Vasella, A. Helv. Chim. Acta, 1979, 62, 2411–2431. b) Madsen, R. Eur. J. Org. Chem.
2007, 399–415, and references cited therein. 3 a) Henon, E.; Bercier, A.; Plantier-Royon, R.; Harakat, D.; Portella, C. J. Org. Chem. 2007, 72,
2271-2278. b) Bercier, A.; Plantier-Royon, R.; Portella, C.. Carbohyd. Res. 2007, 342, 2450-2455.
49
IL13
CARBOHYDRATES AND RADIATION: TOGETHER THEY WORK
Maria H. Casimiro,a,b João P. Lealc,d
(a) Departamento da Química, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal, [email protected]
(b) Unidade de Física e Aceleradores, Instituto Tecnológico e Nuclear, 2686-953 Sacavém, Portugal, [email protected]
(c) Unidade de Ciências Químicas e Radiofarmacêuticas, Instituto Tecnológico e Nuclear, 2686-953 Sacavém, Portugal, [email protected]
(d) Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, 1749-016 Lisboa, Portugal , [email protected]
Chitosan is a biocompatible and biodegradable polysaccharide with an unusual combination of biological activity plus physical and chemical properties, which makes it an important biomaterial for environmental, pharmaceutical and biomedical applications. The work now presented is based on already published data1-3 and on new ones, and concerns the development of biocompatible and microbiologically safe chitosan based polymeric films, which could simultaneously work as wound dressing and support in drug delivery systems.
The films were obtained by γ radiation induced polymerization, after which they had been characterized in order to investigate its application as support in drug delivery systems. Based on microbe inactivation studies and modification of some functional properties the possibility of simultaneous membrane preparation/sterilization was also explored. Obtained data display values within acceptable range of biocompatibility and microbiological safety, as well as a fast drug release kinetic (which is dependent on reticulation degree due γ irradiation, composition and films thickness).
Results point out to a set of biological, physical and chemical properties which allow concluding that the application of the prepared films as “ready to use” drug release system is viable.
1 M.H. Casimiro, J.P. Leal, M.H. Gil, Nucl. Instr. and Meth. B 2007, 265, 406-409. 2 M.H. Casimiro, J.P. Leal, M.H. Gil, Nucl. Instr. and Meth. B 2005, 236, 482-487. 3 M.H. Casimiro, Botelho, M. L., J.P. Leal, M.H. Gil, Rad. Phys. Chem. 2005, 72, 731-735.
50
IL14
HOW CARBOHYDRATE RESEARCH SUPPORTS LOCAL AGRO-FOOD PRODUCTION
Dulcineia Ferreira
CI&DETS, Agricultural Polytechnic School of Viseu, Viseu, 3500-606, Portugal.
[email protected] In the Centre and North of Portugal pears (pyrus communis L.) of a regional variety called S. Bartolomeu are dried according to traditional methodology. The fruit is sun-dried in open air yielding a small pear with reddish brown colour and characteristic flavour and elastic properties – pêra passa de Viseu. To aid the local producers we started a program to better understand the chemical and physicochemical transformations occurring in the pear. In a first phase we had investigated the changes in structure and composition of polysaccharides and phenolic compounds after the drying process and its impact on texture.1,2,3
More recently4 we investigated whether the drying process could be modified. Indeed, the traditional sun-drying at open-air could be experimentally replaced by two different convective drying systems, one with direct solar radiation and another one using heat from low-cost solar collectors. Thus, an improvement of the drying process was achieved by reducing the drying time. On a (macro)molecular level we are studying the changes that occur during processing, and their relation to the stage of ripening and the drying technology. While there are several studies on ripening, little was known on the changes that occur on a (macro)molecular level during dehydration of fruits and vegetables.
The final goal of our project4 is to generate added value for a regional variety of pear to support the local agro-food sector. The creation of a Protected Designation of Origin is presently being prepared with the intervention of the Center of Valorization of Fruits and Vegetables of the Region of BEIRA ALTA (FELBA) and the Minister of Agriculture and Fishery and Rural Development.
1 D. Ferreira, J. A. Lopes da Silva, G. Pinto, C. Santos, I. Delgadillo, M. A. Coimbra, J. European Food Research and Technology 2008, 226 [6], 1545-1552.
2 Ferreira, D.; Guyot, S.; Marnet, N.; Delgadillo, I.; Renard, C. M. G. C.; Coimbra, M. A. J. Agric. Food Chem. 2002, 50, 4537-4544.
3 D. Ferreira, A. Barros, M. A. Coimbra, I. Delgadillo, Carbohydr. Polym., 2001, 45, 175. 4 Project PTDC/AGR-ALI/74587/2006 financed by the Foundation for the Science and the Technology
(FCT) of the Minister of Science, Technology and Higher Education.
51
IL15
OLIVE POMACE BIOREFINERY – CONTRIBUTION OF POLYSACCHARIDES
Manuel A. Coimbra,a,* Susana M. Cardoso,a,b and José A. Lopes-da-Silva a
(a) Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal [email protected] (b) Escola Superior Agrária de Bragança, 5301-855 Bragança, Portugal
Olive fruits are the raw material for a number of products, particularly olive oil and table olives. Olives are picked late in the autumn or winter, depending on the variety and on the desired characteristics of the final product. For olive oil production, the olives are harvested at an early stage of ripening. On the contrary, for table olive production, particularly for black oxidized processing, the olives harvested at different stages of ripening, i.e. green, cherry and, for certain varieties, black, are generally used. At these ripening stages, olives have distinct textures which are greatly determined by structural changes in the cell wall pectic polysaccharides1.
Olive pomace is an industrial by-product originated in the olive oil production process that is obtained by squeezing the olive pulp without any chemical treatment. If water is added to the extraction media, three phases occur: oil, water and pomace. This residue is usually used for the extraction of olive pomace oil with n-hexane. For environmental reasons, the addition of water is avoided in most of the industries. This change in the technology results in a very wet pomace due to retention of water from the fruit in the residue. This residue has no significant commercial value due the considerable energy expenditure required to the drying process. With the purpose to valorise this by-product by defining new applications, we have been characterising the wet olive pomace, namely the structural features and rheological properties of the cell wall polysaccharides and phenolic compounds.
The arabinan moiety of olive pulp pectic polysaccharides has been shown to contain a characteristic structural feature that had never been reported to occur in any other arabinan: a β-anomer of an Araf residue occurs as the terminal residue of the (1→5)-linked arabinan backbone. All other Ara residues are in α anomeric configuration2.
The pectic polysaccharides present in the wet olive pomace are polydisperse in relation to sugar composition and charge due to the high content of arabinose. Despite the high neutral sugar content, this pectic fraction formed elastic gels on addition of calcium, both at pH 7 or pH 3. As compared to a commercial pectin, the olive pectic extract showed higher critical concentrations but also a much larger zone in which homogeneous gels were obtained. The results allowed inferring that olive pomace can be a potential source of gelling pectic material with distinct rheological properties than those available commercially3.
1 Mafra, I., Lanza, B., Reis, A., Marsilio, V., Campestre, C., Angelis, M., Coimbra, M. A. Physiol.
Plantarum 2001, 111, 439-447. 2 Cardoso, S. M., Ferreira, J. A., Mafra, I., Silva, A. M. S., Coimbra, M. A. J. Agric. Food Chem. 2007,
55, 7124-7130. 3 Cardoso, S. M., Coimbra, M. A., Lopes da Silva, J. A. Carbohydr. Polym. 2003, 52, 125-133.
52
IL16
GREEN CHEMISTRY FOR SUSTAINABLE DEVELOPMENT AT L’OREAL: SYNTHESIS OF NEW C-GLYCOSIDES OF LARGE INTEREST IN COSMETICS
Michel Philippe
L’Oreal Recherche, Aulnay-sous-bois, France [email protected]
The description of L’Oreal’s Research and Development and its commitment to green and sustainable chemistry are developed. The latter is directly linked to a socially responsible business (1). L’Oreal’s “green methodology” is based on the basic principles of green chemistry as defined by P. Anastas and J. Warner (2). To develop sourcing innovation, greater emphasis is placed on three main principles:
− the use of renewable raw materials from plants, − the development of environmentally friendly processes, − and the manufacture of low ecotoxicity and biodegradable ingredients.
The company favours the use of renewable raw materials from plants; today, 40% of ingredients used are sourced from renewable plants. Among these raw materials, carbohydrates represent a unique class of compounds as final products or strategic building blocks to have access to new active ingredients in cosmetics. Greater emphasis is also placed on the development of new green technologies. L’Oreal has perfected original green routes (3) to produce C-glycosides of interest in our different applications as amphiphilic derivatives or new skin care active ingredients. These new green routes are discussed in comparison with previous processes. 1 www.LOREAL.com /Our Company/Sustainable Development; 2 Anastas P., Warner J.C., Green Chemistry, Oxford University Press, New York, 1998, p. 30); 3 Lubineau A. et al., Chem. Commun., 2000, 2049-2050;
Dalko M., Breton L., WO 2002051828 (L’OREAL); Philippe M., Semeria D., WO 2002051803 (L’OREAL); Hersant Y. et al., Carbohydrate Research 339 (2004) 741-745.
53
IL17
GREEN SUGAR-BASED SURFACTANTS AND MONOMERS FROM MARINE RESOURCES
Thierry Benvegnu,a* Myriam Roussel,a Daniel Plusquellec,a Jean-François Sassi,b† Hervé Le Deit,b
Johann Hendrickx,b Yannick Leratb
(a) CNRS UMR 6226, Equipe Chimie Organique et Supramoléculaire, Ecole Nationale Supérieure de Chimie de Rennes, Campus de Beaulieu, 35700 Rennes, France, * [email protected]
(b) CEVA – Centre d’Etude et de Valorisation des Algues, presqu’île de Pen Lan, 22610, Pleubian, France. † [email protected]
The development of green surfactants based on natural renewable resources is a concept that is gaining recognition in detergents and cosmetics.1 This new class of biodegradable and biocompatible products is a response to the increasing consumer demand for products that are both "greener", milder and more efficient. In order to achieve these objectives, it is necessary to use renewable low-cost biomass that is available in large quantities and to design through green processes molecular structures that show improved performance, favorable ecotoxicological properties and reduced environmental impact. Within this context, marine algae represent a rich source of complex polysaccharides and oligosaccharides with innovative structures and functional properties that may find applications as starting materials for the development of green surfactants and cosmetic actives. The Ecole Nationale Supérieure de Chimie de Rennes (ENSCR) and the Centre d’Etude et de Valorisation des Algues (CEVA) in Brittany (France) have developed original surfactants based on alginates (cell-wall polyuronic acids from brown seaweeds) or ulvans2 (sulfated rhamnouronans from the cell wall of green seaweeds) and fatty hydrocarbon chains derived from vegetable resources.3,4 Controlled chemical and/or enzymatic depolymerizations of the algal polysaccharides give saturated and/or unsaturated functional oligosaccharides incorporating rare sugars such as uronic acids (mannuronic, guluronic, iduronic, glucuronic acids) and sulphated rhamnose. The functionalization of these oligosaccharides through transesterification / transglycosylation processes in fatty alcohols is solvent-free and yields anomerically pure derivatives. Aqueous basic and acid treatments lead to anionic or neutral single-tailed surfactants (efficient interfacial and foaming properties). Additional structural variations (bola lipids5, double-tailed surfactants2) are proposed as expansions of the classical single-tailed molecules for the preparation of emulsifying agents and stable drug delivery systems. Macromolecular surfactants with associative behaviour were also developed, out of vegetable oil and ulvan polymer extracted green seaweeds.6 These surfactants are biodegradable in seawater and have been tested as dispersants for oil-spills.
1 Benvegnu, T.; Plusquellec, D.; Lemiègre, L.;Belgacem, M. N.; Gandini, A., Surfactants from
Renewable Sources: Synthesis and Applications. In Monomers, Polymers and Composites from Renewable Resources, Eds. Elsevier Limited: Amsterdam, 2008.
2 Lahaye, M., Robic, A., Biomacromolecules 2007, 8,1765-1774 3 Roussel, M., Benvegnu, T., Lognoné, V., Le Deit, H., Soutrel, I., Laurent, I., Plusquellec, D., Eur. J.
Org. Chem. 2005, 3085-3094 4 CEVA - Unpublished results 5 Roussel, M., Lognoné, V., Plusquellec, D., Benvegnu, T., Chem. Commun. 2006, 3622-3624 6 WO 2007/045795: Product resulting from the grafting of fatty chains to ulvans and use of said
product as a surfactant.
54
IL18
CARBOHYDRATES IN PHARMACEUTICAL INDUSTRIES
Hans Peter Wessel
F. Hoffmann-La Roche Ltd., Pharmaceutical Research, Discovery Chemistry CH-4070 Basel, Switzerland [email protected]
Carbohydrates and their derivatives are being employed in pharmaceutical industries in research and in production, be it as small molecules, natural products, or biologicals. Research applications include the use as chiral pool starting materials e.g. to furnish peptide mimetics or chiral scaffolds for the generation of compound libraries. Bioactive carbohydrates are being studied intensely, and some of those or their mimetics1 have progressed to the market. Specific examples will be discussed.
1 Wessel, H.P.; Lucas, S.D. Oligossacharide mimetics. In Glycoscience: Chemistry and Chemical Biology; Fraser-Reid, B.; Tatsuda, K.; Thiem, J., Eds.; Springer Verlag: Heidelberg 2008, Part 9, 2079-2112; (b) Wessel, H.P. Saccharide-peptide hybrids. In Oligosaccharides in Chemistry and Biology: A Comprehensive Handbook. Synthesis of Oligosaccharides, Glycoconjugates and Glycomimetics, Part II: Synthesis of Oligosaccharide Mimetics; Ernst, B., Hart, G., Sinay¨, P., Eds.; Wiley/VCH: Weinheim, 2000; Vol. I, 565–586.
55
IL19
CALIXARENE-BASED GLYCOSIDE CLUSTERS AS POTENTIAL ANTIVIRAL DRUGS
Alberto Marra
Dipartimento di Chimica, Università di Ferrara, Via Borsari 46, 44100 Ferrara, Italy, [email protected]
The carbohydrate-protein interaction is a key step in the cell-cell, cell-bacteria, and cell-virus recognition process. In order to compensate for the usually low affinity of monovalent carbohydrate for proteins, a cooperative binding of multiple copies of ligands and receptors takes place in living organisms. We prepared1 tetra- and octavalent sialoside clusters in good yields exploiting for the first time the multiple copper-catalyzed cycloaddition of a propargyl thiosialoside with upper and lower rim calix[4]arene polyazides. The cycloadducts featured the hydrolytically stable carbon-sulfur bond at the anomeric position and the 1,4-disubstituted triazole ring as the spacer between the sialic acid moieties and the platform. These multivalent sialosides did not manifest cytotoxicity and inhibited, at submillimolar concentrations, the hemagglutination and the viral infectivity mediated by the influenza virus.
O OO O
N
NN
CO2H
O
S
OHNHAc
HO
HO
HO
N N
N
N
NN
NN
N
CO2H
OS OH
NHAcOH
HO OH
CO2H
O S
HO
AcHN
OHHO
HO
HO2C
O
S
HONHAc
HOHO OH
N
NN
NN
NN
NN
N
NN
CO2H
O S
HO
AcHN
OHHO
HO
CO2H
OS OH
NHAcOH
HO OH
CO2HO
S
HO
AcHN
OHOH
HO
HO2CO
S
HO NHAc
OH
OHOH
1 Marra, A.; Moni, L.; Pazzi, D.; Corallini, A.; Bridi, D.; Dondoni A. Org. Biomol. Chem. 2008, 6,
1396-1409.
56
IL20
BACK TO MY ROOTS: NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF TYPE-2 DIABETES FROM AN ANCIENT HERBAL REMEDY
B. Mario Pinto
Department of Chemistry, Simon Fraser University, Burnaby, B.C. V5A 1S6 Canada, [email protected]
The synthesis of a new class of zwitterionic glycosidase inhibitors from a natural plant source will be described. These compounds comprise a sulfonium ion with an internal sulfate counterion. Modification of the parent natural compound, salacinol, has yielded a variety of analogues as candidate inhibitors, some of which have subsequently been isolated from the plant source. Synthetic studies towards the stereochemical structure elucidation of another compound, kotalanol, from the same plant source will also be described. Structure activity relationships in vitro with recombinant human maltase glucoamylase, a critical enzyme involved in the post-amylase breakdown of carbohydrates in the small intestine, provide insight into the requirements of an effective inhibitor. These predictions have been subsequently verified by X-ray crystallography of the enzyme-inhibitor complexes. In addition, the latter studies confirm the original hypothesis that these inhibitors interact with the enzyme active site through stabilizing electrostatic interactions with the catalytically-active carboxylate residue. Finally, in vivo studies in rats with selected compounds show control of plasma glucose and insulin levels, thus providing lead candidates for the control of Type 2 diabetes.
57
IL21
BIOPROCESSING OF NATURAL PRODUCTS WITH GLYCOSIDASES
Vladimír Křen,* Lenka Weignerová, Petr Marhol Institute of Microbiology, Centre for Biocatalysis and Biotransformation, Czech Academy of Sciences,
Vídeňská 1083, CZ 142 20 Praha 4, Czech Republic; [email protected] Numbers of biologically active natural products are glycosides. Often, the glycosidic residue is crucial for their activity, in other cases glycosylation only improves pharmacokinetic parameters.1,2 Recent developments in molecular glycobiology brought better understanding to the aglycone vs. glycoside activities.3 Enzymatic modification of these glycosides - both extension of the glycoside moiety and its selective trimming - is advantageous due to selectivity and mildness of the reaction conditions in presence of reactive and sensitive, complex aglycones. Moreover, enzymatic reactions enable to use resulting products as “natural products”, e.g. in nutraceuticals.4
Selective trimming by glycosidases will be demonstrated on the large-scale production of the high-value nutraceutical flavonoid quercetin-3-β-D-glucopyranoside (isoquercitrin) from rutin by using α-L-rhamnosidase. Resulting compound is valuable antioxidant and antiallergic substance void of potential toxicity of quercetin.
Second approach, e.g. extension of the existing glycoside by the enzymatic action will be demonstrated on the example of flavonolignan silybin glycosides generating thus substances with improved pharmacokinetic parameters and with specific targeting to the liver tissue. Silybin and its derivatives experience now a boom both in science (over 100 papers/y.) and in novel medicinal applications as, e. g., prostate cancer treatment, liver regeneration and some others.6
Acknowledgements
This work was supported by the grants from the Czech Ministry of Education LC06010, OC08049 and Czech Science Foundation GA303/08/0658. 1 V. Křen, L. Martínková: Glycosides in medicine: "The role of glycosidic residue in biological activity".
Curr. Med. Chem. Rev. 8, 1313–1338 (2001). 2 V. Křen: Glycoside vs. aglycon “The role of glycosidic residue in biological activity”, Fraser-Reid ed.
Glycoscience, Springer, 2008. 3 V. Křen, T. Řezanka: Sweet antibiotics – the role of glycosidic residues in antibiotic and antitumor
activity and their randomization. FEMS Microbiol. Reviews 32, 858-889 (2008). 4 D. Monti, A. Candido, M. Manuel Cruz Silva, V. Křen, S. Riva, B. Danieli: Biocatalyzed generation of
molecular diversity: Selective modification of the saponine asiaticoside. Adv. Synth. & Catal. 347, 1168-1174 (2005).
5 V. Křen, L. Cvak, P. Sedmera, V. Šimánek, J. Ulrichová, J. Stuchlík: Silybin glycosides and the method of the preparation. Czech patent No. 287657, 8.11. 2000.
6 R. Gažák, D. Walterová, V. Křen: Silybin and silymarin – new and emerging applications in medicine. Curr. Med. Chem. 14, 315-338 (2007).
58
IL22
THE USE OF MICROBIAL POLYSACCHARIDES AS VACCINES – POSSIBILITIES, PROBLEMS AND PROSPECTS
Stefan Oscarson
Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology,
University College Dublin, Belfield, Dublin 4, Ireland [email protected] Vaccines based on bacterial capsular polysaccharides are an important part of immunization schemes all over the world. The pure polysaccharide vaccines, however, have some major drawbacks and the newly licensed vaccines are of the conjugate vaccine type, i.e. the saccharide portion is conjugated to a carrier protein, which has proven to be very effective and safe. Sometimes, however, there are problems also with this approach, e.g. lability, heterogeneity or molecular mimicry of the polysaccharide structure. A survey of existing commercial polysaccharide-based vaccines will be presented and the pros and cons of the various constructs discussed. New techniques to try to solve still existing problems will also be presented.
59
IL23
COMPUTATIONALLY-GUIDED GLYCOSCIENCE: TOWARD THE RATIONAL DEVELOPMENT OF CARBOHYDRATE-BASED ANTI-VIRAL THERAPEUTICS
Robert J. Woods
University of Georgia, Complex Carbohydrate Research Center, 315 Riverbend Road, Athens, GA 30602, [email protected]
Hemagglutinin (HA) mediates attachment to, and entry of, influenza virus into host cells by binding to sialic acid receptors at the cell surface. Human influenza viruses preferentially bind to sialic acid linked to galactose by α-2,6 linkages; the main type found on the epithelial cells of the human upper respiratory tract. Avian viruses tend to bind to α-2,3 linkages that are found predominantly on avian intestinal epithelium1. All influenza A viruses that have infected mammals emerged as some point from avian species2. Changes in the amino acid sequence of HA can alter the sialic acid specificity of influenza viruses, with the change of one or two amino acids3 being sufficient to change the receptor binding specificity and affect interspecies transmission barriers. Computational methods can be employed both to predict strain specificity, and to potentially to develop carbohydrate-based anti-adhesive (anti-viral) agents. Here we examine the use of automated docking algorithms (AutoDock)4 and molecular dynamics simulations with the GLYCAM force field5 of human and avian receptor – HA complexes3. The theoretical methods correctly identify the strain preferences for a variety of H1 hemagglutinins and provide insight into the origin of the affinity differences. Notably molecular clustering is found to be a robust descriptor of strain specificity. 1 Wong, S. S.; Yuen, K. Y., Avian influenza virus infections in humans. Chest. 2006, 129, (1), 156-
168. 2 Webster, R. G.; Bean, W. J.; Gorman, O. T.; Chambers, T. M.; Kawaoka, Y., Evolution and ecology
of influenza A viruses. Microbiol. Mol. Biol. Rev. 1992, 56, (1), 152-179. 3 Gamblin, S. J.; Haire, L. F.; Russell, R. J.; Stevens, D. J.; Xiao, B.; Ha, Y.; Vasisht, N.; Steinhauer,
D. A.; Daniels, R. S.; Elliot, A.; Wiley, D. C.; Skehel, J. J., The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin. Science 2004, 303, 1838-1842.
4 Morris, G. M.; Goodsell, D. S.; Huey, R.; Hart, W. E.; Halliday, S.; Belew, R.; Olson, A. J. Autodock, 3.0.5; Scripps Research Institute: La Jolla, 1999.
5 Kirschner, K. N.; Yongye, A. B.; Tschampel, S. M.; Daniels, C. R.; Foley, B. L.; Woods, R. J., GLYCAM06: A Generalizable Biomolecular Force Field. Carbohydrates. J. Comput. Chem. 2008, 29, 622-655.
60
IL24
CARBOHYDRATE-ANALYSIS: LIQUID CHROMATOGRAPHY TO SOLVE A CHALLENGE
Cees Bruggink,a* and Detlef Jensenb
(a) Dionex Benelux BV, Abberdaan 114, 1046 AA Amsterdam, Netherlands,
(b) Dionex (Europe) Managment AG, Solothurnerstrasse 259, CH-4600 Olten, Switzerland Carbohydrates in their variety and complex chemical composition play an important role in chemical processes, in pharmaceutical industry, Food and Beverage and many others. The common necessity of the mentioned market segments and applications is to analyze the carbohydrates for both quantification and structural information to understand properties. Compared to spectroscopy (e.g. NMR), or compared to separation techniques requiring derivatization (e.g. GC), modern liquid chromatographic techniques (LC) allow for the direct analysis of native and derivatized carbohydrates. Methods such as GPC, HILIC, Reversed Phase and Ion exchange chromatography can be used to gather information about carbohydrates in complex mixtures. This presentation will cover the different application areas, showing examples for different separations. We will discuss the use of different approaches depending on the specific analytical question. One focus will be on the separation technique used, as well as on the detection scheme, like MS-hyphenation and modern electrochemical approaches.
61
IL25
FUNCTIONAL FOOD INGREDIENTS FOR GUT HEALTH: EXPLOITATION OF PLANT BIOMASS SOURCES FOR NOVEL INGREDIENTS
Robert Rastall
Department of Food Biosciences, The University of Reading, PO Box 226, Whiteknights, Reading,
RG6 6AP. [email protected] Recent years have seen an increase in interest, both in the scientific community and in industry, in the development of functional foods. These are foods with specific health attributes beyond nutrition. One of the most rapidly developing sectors is foods targeted at gut health. Traditionally, live bacterial supplements, or probiotics, have been used in this regard. A more recent concept, however, is that of prebiotics. These are non-digestible carbohydrates which are selectively fermented in the gut by specific bacterial groups which convey health benefits. The current market in the EU is dominated by inulin, largely from chicory, and fructo-oligosaccharides derived either from inulin by hydrolysis or from sucrose by synthesis. A smaller market share is occupied by galacto-oligosaccharides derived from lactose. There are now many studies substantiating the prebiotic status of these ingredients and increasing data on the impact they have on human health. There is, however, potential to derive functionally enhanced forms of prebiotics. Such functional enhancements may include the ability to inhibit pathogens from binding to host cells, ability to regulate the growth cycle of cells, more selective targeting at specific bacterial groups and increased persistence in the colonic environment. A potential source of such enhanced prebiotics is plant biomass. There are many sources of plant biomass from a range of agricultural activities and food processing operations. These represent a rich resource of carbohydrate chemistry which can be exploited to manufacture novel prebiotics. This lecture will give an overview of the prebiotic concept in human health and nutrition and then focus on the potential to derive bioactive oligosaccharides from biomass sources. Recent data will be presented from our studies on pectins and pectic oligosaccharides, and on cereal-derived oligosaccharides.
62
IL26
DIFRUCTOSE DIANHYDRIDE-ENRICHED CARAMELS: PREBIOTIC AND NUTRACEUTICAL PROPERTIES
Carmen Ortiz Mellet,a* Julio Gálvez,b Antonio Zarzuelo,b Raquel Ruiz,c Luis A. Rubio,c and José M. García Fernandezd
(a) Dpto. de Química Orgánica, Facultad de Química, Univ. Sevilla, Sevilla E-41012, Spain, *[email protected]
(b) CIBER-EHD, Departamento de Farmacología,Univ. Granada, Spain. (c) Animal Nutrition Unit, Estación Experimental del Zaidín, CSIC, Armilla 18100, Granada, Spain.
(d) Instituto de Investigaciones Químicas, CSIC - Univ. Sevilla, E-41092 Sevilla, Spain.
Caramelization commonly occurs when sugars, or products containing a high proportion of sugars, are heated either dry or in concentrated aqueous solutions, alone or in the presence of certain additives. Besides its traditional involvement in the preparation of home-made products, caramelization is an important industrial process used for the preparation of food products and coloring additives. Upon thermal treatment of sugars, dehydration and self-condensation reactions occur, giving rise to volatiles (principally 2-hydroxymethylfurfural, HMF), pigments (melanoidines) and oligosaccharidic material. In 1994, di-D-fructose dianhydrides (DFAs) were identified as the major components of the oligosaccharide fraction,1 which also contains glycosylated-DFAs of different DP. While DFAs have been known for a long time, it was ignored that they are actually present in the human diet. Up to 14 different DFA diastereomers have been identified in sucrose caramel, amounting for 10-20% of the non-volatile material.2 The literature in the field points to a beneficial effect associated to DFA consumption. We have now developed a caramelization technology that allows producing caramels with up to 70-80% DFAs and glycosyl-DFAs by controlled heating of a commercial sugar precursor, preferentially D-fructose, in the presence of a heterogenous acid catalyst.3 The composition of the products is determined by GC using pure standards obtained by chemical synthesis.4 Evaluation of the prebiotic properties of the new caramels has been carried out first in female Wistar rats. In healthy animals fed DFA-enriched caramels, the counts of lactobacilli in the colonic contents and short chain fatty acid production were slightly increased in comparison with untreated control rats. The absence of any toxic effect exerted by these products was also confirmed. Most interestingly, in animals with trinitrobencenesulphonic acid-induced colitis, a model for human Crohn´s disease, amelioration in the macroscopic colonic damage as well as a recuperation of the counts of the beneficial colonic bacteria in the intestinal contents were observed. More recently, in vitro experiments with the colonic content of pigs demonstrated an increase in the counts of bifidobacteria and lactobacilli accompanied by a decrease in enterobacteria and coliform bacteria, supporting a prebiotic activity. 1 Defaye, J.; García Fernández, J. M. Carbohydr. Res. 1994, 256, C1-C4. 2 Ratsimba, V.; García Fernández, J. M.; Defaye, J.; Nigay, H.; Voilley, A. J. Chromatogr. A 1999, 844,
283-293. 3 Rubio Castillo, E. M.; Gómez-García, M.; Ortiz Mellet, C.; García Fernández, J. M.; Zarzuelo Zurita,
A.; Gálvez Peralta, J. J.; Duval, R. “New caramels with high content in prebiotic oligosaccharides, their preparation and use”. ES/P200700675, 2007; PCT/ES2008/000129, 2008.
4 Garcia-Moreno, M. I.; Benito, J. M.; Ortiz Mellet, C.; García Fernández, J. M. Molecules 2008, 13, 1640-1670.
63
IL27
STUDIES ON THE STRUCTURE OF POLYSACCHARIDES
Johannes F.G. Vliegenthart
Bijvoet Center, Utrecht University, Utrecht, The Netherlands, [email protected] In many organisms polysaccharides have a protective function as to the integrity of the living cell and with respect to the environment. This is seen for example in plants, where cellulose is prominently present, chitin is a main constituent of crustaceans and insects, in yeasts different glucans may be found, in a number of bacteria the exopolysaccharides are important components. In addition numerous polysaccharides occur with various biological functions. Many of the natural polysaccharides have found industrial application. A few examples will be given. For cellulose and starch as well as for their derivatives, this is obvious. Several bacterial exopolysaccharides are applied in industry, because of the effects of these compounds on viscosity and gel forming e.g. in mining processes. Polysaccharides produced or excreted by organisms with a GRAS (generally recognized as safe) status are widely used in food industry. The pharmaceutical industry has interest in some polysaccharides as potential anti-cancer agents, as starting material for the preparation of vaccines and as biodegradable scaffolds in regenerating tissues.
The relation between structure and physical properties is an important question to address. With this aim the structure of several polysaccharides was studied in our laboratory. However, so far no clear relation between primary structure and physical properties was disclosed. Probably, knowledge of the three-dimensional structure in solution provides a better tool to make further progress. The understanding of the physical behavior of polysaccharides in complex systems like food or in nature in cell walls requires in addition insight into the interactions with other biopolymers like other polysaccharides and proteins, associations with lipids and binding of metal ions. pH and temperature have influences as well.
Determination of the structure of polysaccharides is rather complicated and usually achieved by a combination of methods. The simplest structures to establish are heteropolysaccharides consisting of repeating units. Irregular heteropolysaccharides pose difficult problems. Homopolysaccharides built up from one type of monosaccharide, but with two or more types of glycosidic linkages are extremely complex to analyze. A few examples will be given of studies carried out in Utrecht.
64
IL28
COMMERCIALIZATION MODELS OF POTENTIAL GLYCOPRODUCTS
Károly Ágoston,* Inge Lundt, Joachim Thiem, Arnold Stütz, István Bajza, Lars Kröger, Gyula Dékány
Glycom A/S; Building 201, Danish Technical University, Lyngby, 2800 Kgs, Denmark;
Establishment of Glycom A/S followed by commercialization efforts of several potential carbohydrate type products will be presented. IP platform required for efficient business development will be outlined. The following projects and their commercialization activities will be discussed in details: 1,5-Anhydrofructose Scientific background, biological activities, potential application fields, novel synthetic technologies suitable for the production of 1,5 anhydrofructose and commercialization actions will be described. Glycomatrix A novel concept for the generation of diversities in the synthesis of complex oligosaccharides via the use of novel glycomatrices will be introduced. Selective human insulin glycosylation and cell surface engineering via novel ligation technologies. Novel glycoligation methodologies, their applications in therapeutic protein modification by using a human insulin model will be explored. Furthermore, the utility of a novel glycoligation in cell surface modification within immunology will be discussed by delivering carbohydrate epitopes to cells. Technology development of human milk oligosaccharides Glycom’s outstanding technology success in manufacturing of human milk oligosaccharides will be presented. Scientific breakthroughs, kg-laboratory studies, pilot plant and industrial productions of key building blocks and selected human milk oligosaccharides will be outlined.
65
IL29
INFLUENCE OF ANOMERIC CONFIGURATION AND GLYCOSIDIC LINKAGE ON THE SOLUTION CONFORMATIONAL ENTROPY OF OLIGOSACCHARIDES
André M. Striegel
Department of Chemistry & Biochemistry, Florida State University
Tallahassee, FL 32306-4390 USA [email protected] We often refer to size-exclusion chromatography (SEC) as an entropically-driven technique, without giving the matter much thought. However, if it is true that separation in SEC is due to an entropic difference between phases, it stands to reason that SEC should then be able to provide entropic information about analytes. There are some restrictions on obtaining this type of information, however: Analytes must be perfectly monodisperse and enthalpic contributions to the separation must be virtually absent. The first requirement restricts this application of SEC to oligomers and select biopolymers, as all synthetic polymers possess some degree of polydispersity. Here, we show how SEC using a single concentration-sensitive detector can be used to measure the solution conformational entropy of oligosaccharides. Anomeric configuration and glycosidic linkage are shown to individually affect the flexibility of various oligosaccharide series under aqueous, quasi-physiological conditions of temperature and pH. Chromatographic results have been augmented by calculations using molecular dynamics computer modeling methods and the influence, or lack thereof, of enthalpic contributions to the separation has also been addressed.
66
IL30
MARINE POLYSACCHARIDES AEROGELS: MATERIALS FOR CATALYSIS AND ADSORPTION
Françoise Quignard
Institut Charles Gerhardt, Matériaux Avancés pour la Catalyse et la Santé, UMR 5253 CNRS-UM2-
ENSCM-UM1, ENSCM, 8 rue de l’Ecole Normale, 34296 Montpellier Cedex 5, France The introduction of renewable resources in the production of catalyst supports and adsorbent is only possible if the materials intended to replace oil-derived or energy-intensive solids comply with strict requirements, like as high surface area, appropriate surface chemistry and porosity, thermal and chemical stability, and low cost. Aerogels of natural polysaccharides are promising candidates for many applications, as they couple the textural properties of highly accessible materials with the versatile chemistry of hydrocolloids. Hydrocolloid-forming polysaccharides are natural polyelectrolytes able to gelify water when added in tiny amounts. Hydrogels containing 1-2 % polymer and 98-99 % water can be shaped as self-standing spheres or films with good mechanical stability. This property is at the basis both of their natural function as water-storage agents for living organisms as well as of their main application. Natural polysaccharides, albeit known for many years as supports for enzymatic catalysts and gelling agents in aqueous phase, suffer from diffusional limitations, due to the low surface area of the dried materials generally used, xerogels or lyophilised solids. This lecture deals with the proper methods to prepare dry materials which retain the dispersion of the polymer hydrogel, namely polysaccharide aerogels. The materials whose properties are herewith described satisfy most of the appropriate requirements for heterogeneous catalysts and supports: they are stable in most organic solvents and present numerous and diverse surface functionalities (like hydroxy, carboxy or amino groups). Their application in catalysis and adsorption could open substantial markets for products of seaweed harvesting and coproducts of seafood industry and provide a new opportunity to obtain materials from one of the less energy-intensive sources of biomass.
67
IL31
POLYSACCHARIDES TRANSFORMATION, NEW PROCESSES AND TECHNOLOGIES
Camélia Stingaa, David Guérinb and Daniel Samaina
(a)CERMAV-CNRS BP 53 38041 Grenoble cedex 9 France [email protected]
(b)CTP, Domaine universitaire BP 251, Grenoble cedex 9, France Cellulose-based paper and board products are extremely versatile in meeting societal needs because they are relatively inexpensive, biodegradable and easily recycled 1. Because of their hydrophilic character and porous structure however, their use as water, grease and gas barrier packaging products requests imperiously an additional coating with synthetic polymers 2.
Chromatogenic chemistry has been proposed by us 3,4 as an alternative pathway. This reaction occurring in solid gas conditions is able to achieve heterogeneous grafting of long chain fatty acids such as stearic acid at the surface of cellulose fibres in industrial settings.
In this paper, we describe first the application of chromatogenic chemistry to various grades of paper and we show that only limited improvement could be achieved in their water barrier properties and none in their grease and gas barrier properties. We describe then the application of chromatogenic chemistry to paper and boards coated with film forming biocompatible polyols such as starch and Polyvinylic alcohol (PVA). Both families of compounds are known to exhibit good grease and gas barrier properties but only in absence of water. Limited improvement in water resistance was observed though the coating and grafting of starch while outstanding improvement in water, grease and gas barrier properties was recorded through the coating and grafting of PVA. In the third part of this presentation, we show that the barrier properties obtained were entirely due to the chemical reaction between PVA and the fatty acid. The reaction gives rise to a 10 fold “ballooning effect” of the PVA sequences involved which produces unusual supramolecular entities involving alternate sequences of native and stearic acid grafted PVA (Polyvinyl steroyl, PVS). We also show that the barrier properties are closely dependent upon the de-acetylation degree of PVA and of their MW (Figure 2.).
1 Mohanty, A.K., misra, M.,Hinrichsen,G., Macromol.Mater.Eng., 2000, 276/277, 1-24 2 Furuheim,K.M., Axelson,D.E., Nordic Pulp Pap.res.J. 2003, 2, 18 3 Samain, D., PCT patent 98.942743.0 1998 4 Berlioz,S., Singa, C., Condoret, J.S., Samain, D., Int.J. Chem. React. Eng. 2008, 6, A2 1-14
68
IL32
CARBOHYDRATES AS ORGANIC RAW MATERIALS : THE MAJOR CHALLENGES AHEAD
Frieder W. Lichtenthaler
Institut für Organische Chemie, Technische Universität Darmstadt,
64287 Darmstadt, Germany,* [email protected] As our fossil raw materials are irrevocably decreasing - the end of cheap oil is predicted for 20401
- and as the pressure on our environment is building up, the progressive changeover of chemical industry to renewable feedstocks emerges as a foremost necessity. Carbohydrates representing 75% of the renewable biomass, they are by far the major biofeedstocks from which to develop industrially and economically viable products that are to replace those derived from petrochemical sources.2-6
To highlight the major challenges lying ahead, the overview to be presented attempts to trace those carbohydrate-based development lines along which the further exploitation of the key sugars of biomass is likely to proceed, towards bulk or fine chemicals, pharmaceuticals, agrochemicals, high-value-added speciality chemicals, or simply enantiopure building blocks for organic synthesis. 1
Campbell, C. J., Laherrère, J. H. “The End of Cheap Oil”, Sci. Am., March 1998, pp. 60-65. 2
Lichtenthaler, F. W. (Ed.), Carbohydrates as Organic Raw Materials, Wiley-VCH, Weinheim, 1991, 365 pp.
3 Lichtenthaler, F. W. „Unsaturated O- and N-Heterocycles from Carbohydrate Feedstocks“, Acc. Chem.. Res. 2002, 35, 728-737.
4 Lichtenthaler, F. W., Peters, S. “Carbohydrates as Green Raw Materials for the Chemical Industry”, Compt. Rend. Chim. 2004, 7, 65-90.
5 Lichtenthaler, F. W. “The Basic Sugars of Biomass: Availability, Present Non-food Uses and Potential Future Development Lines”, in Biorefineries - Industrial Processes and Products (B. Kamm, P. Gruber, Eds.), Wiley-VCH, Weinheim, 2006, Vol. 2, pp. 3-59.
6 Lichtenthaler, F. W. “Carbohydrates as Renewable Raw Materials: A Major Challenge of Green Chemistry” Methods and Reagents for Green Chemistry (P. Tundo, A. Perosa, Eds.) J. Wiley, Hoboken, NJ, 2007, pp. 23-63.
69
OC1
DESIGN OF AMPHIPHILIC CATALYSTS FOR THE SELECTIVE CONVERSION OF SUGARS
François Jérôme,a* Nicolas Villandier,a Ayman Karam,a Joël Barrault,a Ronan Pierreb and Yves
Queneau.b
(a) Laboratoire de Catalyse en Chimie Organique, CNRS-Université de Poitiers, 40 avenue du recteur Pineau, F-86022 Poitiers, France ; * [email protected]
(b) Laboratoire de Chimie Organique, ICBMS, INSA Lyon, 20 avenue Albert Einstein, F-69621 Villeurbanne, France
Within the framework of green chemistry, utilization of sugar as renewable raw materials has become of growing interest. However, chemical processes involving sugars require chemists to overcome many obstacles such as the thermal instability of sugars, the presence of numerous hydroxyl groups and their low solubility in common organic solvents. In order to circumvent these issues, we specifically designed some basic heterogeneous catalysts and we showed in particular the important role played by the amphiphilicity of the catalytic surface on the reaction selectivity.1 In this context, we report here the catalytic and selective etherification of sucrose with 1,2-epoxydodecane. This reaction was first performed at 110 °C in DMSO and performances, activity and selectivity, of various solid basic catalysts was investigated.
Over highly hydrophilic catalyst (SiO2-NMe2), the fatty 1,2-epoxydodecane was not absorbed and, in this case, a major thermal degradation was observed. Reversely, over hydrophobic catalyst (PS-NMe2), sucrose poorly interacts with the catalyst surface and an important polymerization of 1,2-epoxydodecane occurred on the catalyst surface. Seeking further improvement, we found that amphiphilic catalysts allowed a significant coverage of the catalyst surface by both reactants leading thus to an improvement of the reaction selectivity. Best catalyst was obtained by supporting an amphiphilic basic ionic liquid film on a polystyrene framework (PS-ionic liquid). Such solid catalyst afforded, in one step, more than 88% yield in the desired sucroether. Transposition of this concept to other disaccharides such as trehalose and isomalt® is presented. The regioselectivity of the reaction is also discussed as well as the catalyst recycling and the replacement of DMSO by water which affords definitely greener processes. Finally, in a last part, we will report that such concept can be successfully used for the grafting of fatty amines on hydroxyethylcellulose.2 1 N. Villandier, I. Adam, F. Jérôme, J. Barrault, R. Pierre, A. Bouchu, J. Fitremann, Y. Queneau, J.
Mol. Cat. A, 2006, 259, 67-77. 2 A. Karam, N. Villandier, M. Delample, C. Klein Koerkamp, J.-P. Douliez, R. Granet, P. Krausz, J.
Barrault, F. Jérôme, Chem. Eur. J., 2008, DOI: 10.1002/chem.200801495.
OOH
OHOH
OHO
O
OH
OH
OH
OH
OO
OHOH
OHO
OO
OH
OH
OH
OHOH( )9
+DMSO / 110°C
solid catalyst
solid catalyst yield (%)a
SiO2-NMe2 20PS-NMe2 30 PS-NMe3
+OH- 62PS-ionic liquid 88
a yields are given at total conversionof the 1,2-epoxidodecane
70
OC2
A DUAL PURPOSE IMMOBILIZED BIOCATALYST FOR INULIN AND SUCROSE HYDROLYSIS
Pedro Fernandes*, Marco. P.C. Marques, Stefano Cattorini, Filipe Carvalho, J.M.S. Cabral
Institute for Biotechnology and Bioengineering/Centre for Biological and Chemical Engineering/
Instituto Superior Técnico, Av. Rovisco Pais, P-1049-001 Lisboa, Portugal. [email protected] The present work is focused on the characterization of an immobilized biocatalyst produced by a novel, simple method, for the hydrolysis of inulin and sucrose. Immobilization is based in the use of polyvinylalcohol (PVA), a biocompatible synthetic hydrogel, which can be easily produced in large scale, and displays considerable mechanical resistance, even under intense stirring. A relevant approach to produce PVA-based immobilized biocatalysts, currently implemented at commercial scale, relies on the use of the so-called LentiKats® liquid, which ultimately yields lenticular particles1. This work addresses a modified procedure for the encapsulation of inulinase in PVA capsules from LentiKat® liquid. In this approach, the PVA based hydrogel is extruded to polyethers (viz. PEG, PPG), where gelification occurs almost instantaneously. The feasibility of the method is illustrated by using, as model systems, sucrose and inulin hydrolysis promoted by a commercial inulinase preparation. The most adequate polyether, PEG 600, was reused throughout several immobilization procedures with no apparent lack of efficiency. Upon immobilization, no significant change was observed in the pH/activity profile in either of the systems tested, pH optimum (4.5) remaining unchanged. Temperature runs were limited to an upper limit of 60 ºC, due to melting of the capsules, a phenomenon also observed at 55 ºC in lenticular PVA particles obtained through standard GeniaLab® technology2,3. PVA beads displayed long-term operational stability in repeated stirred, 24-hour batch-mode runs for each model system. In each case 20 consecutive runs were performed at 50 ºC, with a final decay of product yield that did not exceed 20% in the worst case scenario. Initial substrate concentration of 5% (w/v) and 10% (w/v) of inulin and sucrose, respectively, were used. Loss of activity during storage, over a 3 month period, did not exceed 10%. 1 www.genialab.com 2 M. Rebros et al. Enzyme Microb. Technol. 2006 , 39, 800-804. 3 M. Rebros et al. Food Chem. 2007, 102, 784-787.
71
OC3
SELF-ASSEMBLIES OF AMPHIPHILIC CYCLODEXTRINS
F. Djedaïni-Pilarda* , V. Bonneta, M. Rouxb, B. Perlyc
(a) UMR6219, Université de Picardie-Jules Verne, 33 rue Saint-Leu, F-80039 Amiens, France [email protected]
(b) SBPM/DBCM (c) SCM/DRECAM, CEA-Saclay F-91191, Gif sur Yvette France
It has been shown that a high diversity of structure such as vesicles, micelles or even mixed phospholipides/cylodextrin derivatives films can be obtained depending on the structure of the cyclodextrin (CD). For this purpose, a novel class of amphiphilic derivatives based on CDs was considered. They were prepared from a pure phospholipid (DMPE) grafted onto the cyclodextrin core through a spacing arm leading to the phospholipidyl-CDs. On the other hand, peptidolipidyl-cyclodextrins (P-CDs) were designed to induce a very large versatility depending on the nature of the amino-acid, the number and the length of the aliphatic chains and the nature of the cyclodextrin moiety. The purpose of this study is to find out a relationship between the molecular structures of such derivatives and their capacity to interact with model lipid membranes as well as to form supramolecular self-organized structures. Physical characterization of the self-assemblies and interactions of these compounds with membrane systems were investigated using several methods (CMC, light scattering, 31P and 2H NMR, small-angle X-ray scattering). Biological evaluations have been performed by a new approach making use of novel immuno-enzymatic assays. The methylated phospholipidyl derivatives were shown to self-organize in water with low CMC to form fluctuating micellar fibers retaining the inclusion capacity of the cyclodextrin cavity. Methylated phospholipidyl-CDs can form fairly stable films by themselves, the presence of a matrix is not required. These films consist of a highly hydrated bilayers of modified cyclodextrins wich are remarkably thick due to their abundant hydration core. Their ability to cross over the blood brain barrier was shown by a new approach making use of novel immuno-enzymatic assays. Investigations performed on a model system showed that methylated phospholipidyl-CDs can cross over the barrier without destructing it. To our knowledge, this is the very first example of an amphiphilic cyclodextrin able to go through this barrier without breaking its integrity. These methylated phospholipidyl derivatives were also tested for dermatological delivery of xenobiotics. Investigations performed by dynamic light scattering (DLS), optical density measurement (OD) techniques, and 2H NMR experiments allowed to establish whether some of the novel peptidolipidyl-CD derivatives have detergent properties and may solubilize the lipid membrane, or they behave as co-lipids and may insert into biological membranes leading to the formation of lipids micro-domains within the bilayer, through finely-turned intermolecular headgroup interactions at the membrane interface. Insertion into artificial membranes has been monitored by 2H NMR spectroscopy using peptidolipidyl-CDs (mixed bilayer phases: CDs surrounded by four phospholipids). S Moutard, F Djedaïni-Pilard, W. Lujtens, B Perly S Pilard, Rapid Commun. Mass spectrom., 2003, 17, 2535-2540; C Sultanem, S. Moutard, J.J Benattar, F. Djedaïni-Pilard, B. Perly, Langmuir, 2004, 20, 3311-3318; B. Perly, S. Moutard, F. Djedaïni-Pilard, Pharmachem, 2005, 1-2, 4-9; M. Roux, S. Moutard, B. Perly, F. Djedaini-Pilard, Biophysical J., 93, 1620-1629, 2007; F. Djedaini-Pilard, B. Perly, M. Roux, European Biophys. J. 2007 36:861–867; A. Angelova, C. Fajolles, C. Hocquelet, F. Djedaïni-Pilard, S. Lesieur, V. Bonnet, B. Perly, G. Lebas, 2008, J. Colloid Interface Sci., 2008, 322, 304-314.
72
OC4
EFFICIENT TELOMERISATION OF BUTADIENE WITH STARCH
Julien Mesnager,a,b Anne Lambin,a Claude Quettiera and Catherine Pinelb*
(a) Roquette Frères, F-62080 Lestrem, France, (b) Université de Lyon; Institut de Recherches sur la Catalyse et l’Environnement de Lyon; 2 avenue Albert Einstein F-69626 Villeurbanne, France, [email protected]
Industrial use of the cheap and abundant native starch suffers from several drawbacks, such as readily thermal decomposition, retrogradation, and low shear stress resistance. Chemical, physical, or enzymatic treatment can provide useful modifications; in particular, esterification or etherification affords hydrophobic starch derivatives. We have developed a catalytic route based on the telomerization of a diene with native starch. 1 This palladium-catalyzed reaction allowed the formation of an octadienyl chain as the main product via dimerization of two molecules of the 1,3-diene with hydroxyl groups of the starch. 1,3-Butadiene, the simplest diene, is readily available at low cost. In our previous reports, we performed the reaction in the presence of a large excess of butadiene and using an in situ the Pd(OAc)2/ 3TPPTS catalytic system. Here we describe a more efficient catalytic system, starting from a [(π-allyl)PdCl]2 precursor.2
OO
H
H
HO
H
OHH
O
OH
O
H
H
HO
H
HOHH
OH0.4% [( π-allyl)Pd(TPPTS)2]Cl
H OO
H
H
HO
H
OHH
O
OH
O
H
H
O
H
HOHH
OHH
The catalytic system for the telomerisation of butadiene with MeOH in the presence of water was first optimized. The complex prepared from [(π-allyl)PdCl]2 +2 TPPTS was very stable and efficient in the reaction with MeOH in the presence of water, and was applied to the telomerization of butadiene with starch. After screening of several parameters (temperature, nature of solvent, reaction time, pH…), the conversion of butadiene reached 80%.
Characterization of the catalytic systems and their efficacy in the telomerization reactions will be presented.
1 C. Donzé, C. Pinel, P. Gallezot, P.L. Taylor, Adv. Synth. Catal., 2002, 344(8), 906-910 ; A. B. Sorokin, S. L. Kachkarova-Sorokina, C. Donzé, C. Pinel, P. Gallezot, Top. Catal., 2004, 27, 67-76
2 E. Kuntz, A. Amgoune, C. Lucas, G. Godard, J. Mol. Catal. A, 2006, 244, 124; E. Kuntz is acknowledged for a gift of TPPTS
73
OC5
SYNTHESIS OF ACIDIC XYLOOLIGOMER MODEL COMPOUNDS
Wilhelm Herok,a Beatriz Abad-Romero,a Georg Sixta,a Clemens Gruber,a Herbert Sixta,b and Paul Kosma a*
(a) University of Natural Resources and Applied Life Sciences, Department of Chemistry, Muthgasse
18, A-1190 Vienna, Austria, * [email protected] (b) Department of Forest Products, Helsinki University of Technology, Espoo 02015, Finland
4-O-Methyl-D-glucuronic acid (4OMeGlcA) is a frequently found constituent in hard-wood xylans such as beech wood xylan. In the context of utilizing low molecular weight fractions of xylooligomers obtained by degradation of xylans isolated from industrial process liquors, model compounds containing 4OMeGlcA residues were synthesized.1 Starting from allyl β-D-glucopyranoside 1 and appropriate protecting group manipulation, methylation of OH-4 followed by TEMPO-oxidation / esterification eventually provided 4OMeGlcA glycosyl donor 3 as well as the free 4-O-methyl-D-glucuronic acid 2 after full deprotection, respectively. Orthoester formation of peracetylated xylodextrins and selective opening afforded the corresponding glycosyl acceptors to be coupled with glucuronic acid donors. Aldobio- and triouronic acids substituted at position 2 of the reducing end xylose unit display retarded degradation kinetics under alkaline conditions in contrast to model compounds carrying these substituents within the xylan chain.2,3
AcO OO
O
OAcAcO AcO
OAc
OAc
n
OHOH
O
OHOH
OAll
OHO
OHOH
OHMeO
O
O
ClMeO
OBnO
OBnBnO
AcO OO
O
OAcAcO AcO
OH
OAc
n
AcO OO
O
OAcAcO AcO
O
OAc
n
OMeOBnO
O
O
BnO
1
4
2
3
5
n = 1,2
n = 1,2 6
n = 1,2 Bn
Furthermore, sulfation of xylooligomers has been achieved at the distal 4-OH group of xylodextrins in good to fair yields using intermediate stannylene acetal formation followed by treatment with the SO3-dimethylamine complex. In addition, the 4-O-sulfate of methyl β-D-xylopyranoside could be crystallized as its sodium salt hemihydrate.4
OH
OO
OHOH
OO
OH
OMeS
O
O
OH
n = 0 - 2
1 Abad-Romero, B.; Haltrich, D.; Potthast, A..; Rosenau, T.; Sixta, H.; Kosma, P. Macromol. Symp. 2006, 232, 93.
2 Oscarson, S.; Svalmberg, P. J. Chem. Soc. Perkin Trans I 2001, 873. 3 Sartori, J.; Potthast, A.; Rosenau, T.; Hofinger, A.; Sixta, H., Kosma, P. Holzforschung 2004, 58, 588. 4 Abad-Romero, B.; Mereiter, K.; Sixta, H., Hofinger, A.; Kosma, P. Carbohydr. Res. in press. Acknowledgment: Supported by WOOD COMET
74
OC6
POLYSACCHARIDES WITH REACTIVE CARBONYLS: CHEMICAL AND PHYSICAL PROPERTIES
Bjørn E. Christensen,a* and Kåre A. Kristiansena
(a) NOBIPOL, Department of Biotechnology, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway * [email protected]
Polysaccharides may contain reactive keto- or aldehydo groups, mostly attributed to oxidative side reactions during processing, and in some cases arising from specific chemical or enzymatic reactions designed for the purpose of oxidation, for instance periodate. In addition to chemical reactivity, the introduction of carbonyl groups directly or indirectly influence the physical properties, for instance chain flexibility.1,2
The carbonyl profiles of a pectin (‘sphagnan’)3 from Sphagnum moss and some periodate oxidized polysaccharides were assayed by fluorescent labeling or reduction with tritiated borohydride, in combination with multidetector SEC. The tritium incorporation method was preferred for alkali stable polysaccharides, while the CCOA method was most suitable for acid stable polysaccharides with low carbonyl content. The 2-AB method is applicable for all polysaccharides tested with varying carbonyl content; however it lacks the ability to detect ketone functionalities4. Interestingly, periodate oxidized alginate reacted only with one molecule of 2-AB per dialdehyde. Sphagnan displayed a special carbonyl profile, with the highest carbonyl content at high molecular weights.
Recently, periodate oxidation was combined with in vitro epimerization of mannuronan – a special alginate obtained from an epimerase-negative strain of Pseudomonas. In this way, novel alginates were obtained5. Some of their chemical and gelling properties will be discussed.
1 Vold, I.M.N., Kristiansen, K.A., Christensen, B.E. Biomacromolecules, 2006, 7, 2136-2146. 2 Christensen, B.E., Vold, I.M.N., Vårum, K.M. Carbohydr. Polym. 2008, 74, 559-565. 3 Ballance, S., Børsheim, K.Y., Inngjerdingen, K., Paulsen, B.S., Christensen, B.E. Carbohydr. Polym.
2007, 67, 104-115. 4 Kristiansen, K.A., Ballance, S., Potthast, A., Christensen, B.E. Carbohydr. Polym. 2009, In press
(Accepted 8 Oct 2008). 5 Kristiansen, K.A., Schirmer, B.C. Aachmann, F.L., Skjåk-Bræk, G., Draget, K.I., Christensen, B.E.
Unpublished results.
O
+Na-OOC
OH
OH
O+Na-OOC
OH
HO
OO
+Na-OOC
OH
HO
O
O
+Na-OOC
OH
OH
O+Na-OOC
O
O
OO
+Na-OOC
OH
HO
O
IO4-
O
+Na-OOC
OH
OH
O+Na-OOC
O
OO
+Na-OOC
OH
HO
O
NH2
O
NH2
HN
O
H2N
NaCNBH3(2-AB)
Monosubstituted at C2 or C3 (not shown)
75
OC7 SUGARS AND LIGNOSULFONATES RECOVERY
FROM SULFITE PULPING OF EUCALYPTUS GLOBULUS BY THE APPLICATION OF MEMBRANE SEPARATION PROCESSES
José Augusto Restolho1, António Prates2, Maria Norberta de Pinho1, and Maria Diná Afonso1
1Technical University of Lisbon, Instituto Superior Técnico, Department of Chemical and Biological
Engineering, Av. Rovisco Pais, 1, P-1049-001 Lisbon, Portugal 2CAIMA - Indústria de Celulose, S.A., Constância - Sul, P-2250-058 Constância, Portugal
The thin spent sulfite liquor (TSSL) generated in pulp and paper mills is a biomass resource that is usually concentrated and burnt in a steam boiler. Yet, the biorefinery concept may add value to the by-products contained in this liquor.
The general aim of this work was to investigate the application of membrane separation processes to TSSL produced by acidic magnesium-based sulfite pulping of Eucalyptus globulus. Its specific objectives were the separation of the lignosulfonates (LS) from the sugars for subsequent fermentation, the fractionation of the lignosulfonates to produce valuable products, the concentration of the xylose contained in the TSSL, and the concentration of the xylitol produced by xylose fermentation.
Preliminary laboratory experiments were conducted in total recirculation mode, at natural pH and room temperature, using several ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) membranes, namely, Alfa Laval UFX10 pHt, DSS-FS61PP, UFX5 pHt, DSS-GR95PP, DSSETNA01PP, NF97, NF99, NF99 HF, DSS-HR98PP, RO99, Dow Filmtec NF200, NF270, Microdyn-Nadir UP010, UP005, NP010 and NP030.
Only the Microdyn-Nadir UP010 membrane displayed a wide gap between the rejections of lignosulfonates (68%) and total sugars (3%), thereby it appears to fit the dual purpose of fractionating the lignosulfonates and separating the high molecular weight LS from the sugars. The separation of the low-medium molecular weight LS from the sugars contained in the permeate might be accomplished by ion exchange. On the other hand, the Dow Filmtec NF200 membrane is the most promising one to concentrate both xylose and xylitol, bearing in mind its high rejection for sugars (96%).
Concentration experiments at a pilot plant and thorough economic assessments should be carried out to enlighten the technical-economical feasibility of the processes implied.
KEYWORDS: biorefinery; eucalyptus, lignosulfonates; membrane separation processes; pulp and paper; thin spent sulfite liquor; xylose
76
OC8 OXIDATION OF CELLULOSE FROM KRAFT PULP
J. A. Figueiredo,* Ana Paula Duarte, Suzana Martins, Carla Abrantes, M. Isabel Ismael, Rogério
Simões
Research Unit of Textile and Paper Materials, University of Beira Interior, P-6201-001 Covilhã, Portugal ; *[email protected]
Cellulose fibers have several carboxylic groups that play an important role in paper production, since their changes affect the properties of the material. The presence of ionisable groups in the fiber has a significant effect on their swelling and on the strength properties of the paper produced. Most of the paper chemical additives are cationic polyelectrolytes which interact with these groups improving paper machine retention. Chemical modifications of cellulosic materials are usually carried out under conditions that destroy the inherent properties of the fibers, like their strength. Efforts have been made in order to achieve chemically modified cellulose fibers which could preserve their strength properties. In this study, carboxylic groups were introduced to an industrial bleached kraft pulp of Eucalyptus globulus by a catalytic oxidation process using TEMPO (2,2,6,6-tetramethylpiperidine-1-oxy radical), sodium bromide and sodium hypochlorite (Fig. 1).1 The oxidation conditions were optimized in order to increase the amount of carboxylic groups without a significant loss in pulp intrinsic viscosity. The determination of total carboxylic groups introduced in pulp fibers was performed using a conductometric titration method. The obtained results showed that an increase of 12% in the carboxyl groups content of pulp fibers gave rise to improvements of the swelling properties of the pulp, strength paper characteristics and cationic starch retention in paper formation. The oxidized pulp without refining exhibited an increase of 40% in its tensile strength and 50% in tear index and internal cohesion (Scott-bond test).
Figure 1 - Scheme of TEMPO-mediated oxidation of cellulose.1
1 a) Saito, T., Okita, Y., Nge T. T., Sugiyama, J., Isogai, A. Carbohydr. Polym., 2008, 65, 435-440; b) Saito, T.; Isogai, A. Tappi J., 2005, 4, 3-8.
77
OC9
THE PROS AND CONS OF THE DEDICATED UPGRADE OF THE HEMICELLULOSIC SUGAR STREAM IN A BIOREFINERY FRAMEWORK
Luís C. Duarte*, Florbela Carvalheiro, Talita Silva-Fernandes, Francisco M. Gírio
INETI, Departamento de Biotecnologia, Estrada do Paço do Lumiar 22, 1649-038 Lisboa, Portugal; [email protected]
The challenge of the future integrated biorefineries is the full economically utilization of all biomass components with the simultaneously production of fuels and chemicals, preferably of added-value. This can only be achieved by the selective fractionation of the lignocellulosic biomass into its polymeric components, thus increasing their individual upgradeability to enhance the process economics. To reach this goal, the fractionation methods used are of crucial importance. Yet, many of the most widely accepted biochemical biorefineries potential lay-outs, are mainly concerned with cellulose hydrolysis and fermentation and the hemicellulosic fractions are, at best, clamped with cellulose, averting its differential upgrade. Therefore, a change in perspective by which the fractionation processes, as well as the overall biorefinery lay-out, are thought and evaluated is needed.
The objective of this work is to review, compare and discuss the main advantages and bottlenecks of the currently available biomass pre-treatment technologies, particularly those leading to the selective fractionation of hemicelluloses. The advantages and disadvantages of the methods will be analysed foreseeing the added-value products possible to obtain from the hemicellulose path, and the most relevant factors which influence both product yield and consistency. Actually, the chemical composition and structural diversity of hemicelluloses constitutes an opportunity for the production of many chemicals, which has not yet been fully exploited. The integration of potential added-value products, e.g. oligosaccharides, polyols, and enzymes in a biorefinery framework will also be presented and discussed based on data for the upgrade of agro-food industrial residues and by-products. Examples will compare the use of mild processes for the selective recovery of hemicelluloses such autohydrolysis and dilute acid hydrolysis of brewery’s spent grain, wheat straw, and eucalypt wood and the biotechnological processing of the hydrolysates. It is foreseen that hemicellulose-derived chemicals will become an ever more relevant category of products, as they hold a promise of economic benefit for the biorefineries.
78
OC10
NOVEL POLYAMIDES FROM DISACCHARIDE-DERIVED DICARBOXYLIC ACIDS
Eckehard Cuny,* Frieder W. Lichtenthaler
Institut für Organische Chemie, Technische Universität Darmstadt, D-64287 Darmstadt, Germany, *[email protected]
As carbohydrates represent 75% of the annually renewable biomass, their utilization for the generation of chemicals and materials that can replace those from fossil resources is a major challenge of green chemistry.1,2 Polyamides being particularly attractive in this context, the disaccharide diacids 2 (from sucrose), 4 (isomaltulose), and 5 (melibiose) were evaluated as acid components after developing practical, large-scale adaptable protocols for their acquisition. Reaction of their dimethyl esters, e. g. 3, with long-chain amines provides diamides with distinct liquid crystalline properties, whilst diamines such as hexamethylene- or phenylene-diamine lead to polyamides of type 6 and 7. The potential application profiles of these products are being presented.
H
O NO
H
HOHO O
OH
OH
O
O
O
H
HNO NO
H
HOHO O
OH
OH
O
O
O
C6H4(NH2)2
R
H
HOHO O
OH
OH
O
O
O
COOHR2
HOHOR1 O
O
MeOH, H+
Pt/O21 R = CH2OH (sucrose)2 R = COOH3 R = COOMe
R
O COOH
4 R1 = OH; R2 = H5 R1 = H; R2 = OH
NH
nn6 7
H2N(CH2)6NH2
66' 6'
6
HO
HO HO
1 Lichtenthaler, F. W.; Peters S., “Carbohydrates as Green Raw Materials for the Chemical Industry”, Comptes rendus Chimie 2004, 7, 65-90. 2 Lichtenthaler, F. W. “The Basic Sugars of Biomass: Availability, Present Non.food Uses and
Potential Future Development Lines”, in Biorefineries–Industrial Processes and Products (B. Kamm, P. Gruber, Eds.), Wiley-VCH, Weinheim, 2006, Vol. 2, pp. 3-59.
79
OC11
ISOSORBIDE: A “SUSTAINABLE DIOL” DERIVED FROM SORBITOL FOR THE SYNTHESIS OF NEW AMPHIPHILES
Valérie Molinier*, Ying Zhu, Morgan Durand and Jean-Marie Aubry
LCOM - UMR CNRS 8009 - Oxydation et Physico-Chimie de la Formulation,
Ecole Nationale Supérieure de Chimie de Lille, F-59652 Villeneuve d'Ascq, France, *[email protected]
Isosorbide (1,4:3,6-dianhydro-D-glucitol) is readily obtained from sorbitol via a double dehydration and is thus an important product of the starch industry. Mono- and di-nitroisosorbide are derivatives used for their vaso-dilating properties and dimethylisosorbide (DMI) is a co-solvent already on the market for cosmetic applications mainly.
In the present work, isosorbide has been used as a polar synthon for the design of various new amphiphilic species (figure 1).
OH
CiO
O
O i = 4,5,6
OE3
C12O
O
OOSO3Na
C12O
O
O
Solvo-surfactants CiIso Non-ionic surfactant C12IsoE3 Anionic surfactant SDIsoS
Figure 1: Amphiphilic derivatives of isosorbide under study
The amphiphilic and hydrotropic properties of the short-chain monoalkyl derivatives (CiIso) have been evaluated. These compounds appear to be efficient “solvo-surfactants”1,2 and could find applications in a wide variety of industrial fields, as for instance the detergent industry. Isosorbide has also been evaluated as a linker building block for the synthesis of two “elongated” surfactants, a non-ionic one (C
12IsoE
3) and an anionic one (SDIsoS). The
insertion of an isosorbide moiety between the lipophilic tail and the hydrophilic tail reveals to have a limited impact in the case of C
12IsoE
3, as regards to the phase behaviour in water,
whereas SDIsoS exhibits very good foaming properties, in comparison with the widely-used sodium dodecyl sulfate (SDS).
1 Bauduin, P., Renoncourt, A., Kopf, A., Touraud, D., Kunz, W. Langmuir 2005, 21, 15, 6769-6775. 2 Zhu, Y., Durand, M., Molinier, V., Aubry, J.-M. Green Chem. 2008, 10, 532-540.
80
OC12
AN INNOVATIVE AND OPTIMIZED SOL GEL IMMOBILIZATION TECHNIQUE FOR GLYCOSIDES ENZYMATIC HYDROLYSIS
Helder Vila-Real, António J. Alfaia, António T. Calado, Maria H.L. Ribeiro*
Institute for Medicines and Pharmaceutical Sciences (i-Med), Faculdade de Farmácia, University of
Lisbon, Av. Prof. Gama Pinto, P-1649-003 Lisbon, Portugal; [email protected]
In recent years there has been a growing interest for the health benefits of glycosides due to their important properties such as anti-oxidant, anti-inflammatory, anti-demential and anti-carcinogenic. The sugar residue is important for their activity, although in some cases deglycosylation improves the biological activity. In this work a biocatalytic system was chosen to enable the deglycosylation of glycosides towards biomolecules, with improved biological activity. Naringinase (an enzyme complex consisting of α-L-rhamnosidase and β-D-glucosidase activity) was the enzyme used. Naringin, the substrate used in this bioconversion, and the product, its aglycone, naringenin, are healthy compounds with biological and pharmacological activities, such as anti-oxidant, anti-inflammatory and anti-cancer, showing a high potential in the pharmaceutical industry. Studies regarding immobilization of naringinase on polymer matrices, k-carrageenan1, calcium alginate2, and the re-usability of the immobilized enzyme have been reported. Sol-gel, an innovative and economical technique for naringinase immobilization in aqueous media was developed. Different sol-gel precursors (tetramethoxysilane, TMOS, methyltrimethoxysilane, MeTMOS, 3-Aminopropyl-trimethoxysilane, APTMOS, diglyceryl silane, DGS) at different aging time were tested in five consecutive re-utilizations. The best results were obtained with TMOS, 4 h aging time, TMOS and glycerol, DGS, 14 h aging time and TMOS/DGS, 4 h aging time. In order to optimize these four matrix, the effects of enzyme concentration, pH, reutilization and aging type system on immobilization efficiency were evaluated. These matrix were characterized regarding temperature, pH, naringin and naringenin partition coefficient and isotherms. The operational stability of bioencapsulated naringinase in the different sol-gel matrices was studied through fifty successive re-utilizations; 100% of residual activity remains constant for the best matrix obtained. Naringinase deactivation followed the Sadana model3.
1 Ribeiro I.A., Ribeiro M.H.L. J. Mol. Catalysis B: Enz. 2008, 51, 10–18. 2 Pedro, H.A., Alfaia, A.J., Marques, J., Vila-Real, H.J., Calado, A.T., Ribeiro, M.H. L., Enz. Microb.
Technol. 2007, 40, 442-446. 3 Sadana A, Henley JP. Enzyme Microb Technol, 1985, 7, 50-60.
81
OC13
ENGINEERING TRANSGLUCOSIDASES REGIOSPECIFICITY FOR PROGRAMMED CHEMO-ENZYMATIC SYNTHESIS OF COMPLEX BACTERIAL
CARBOHYDRATES
Elise Championa-c, Julien boutetd, Karine Descroixd, Claire Moulisa-c, Sandrine Morela-c, Pierre Monsana-c, Laurence A. Mulardd, Magali Remaud-Siméona-c and Isabelle Andréa-c
(a) Université de Toulouse; INSA,UPS,INP; LISBP, 135 Avenue de Rangueil, F-31077 Toulouse, France
(b) CNRS, UMR5504, F-31400 Toulouse, France (c) INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, F-31400 Toulouse, France
(d) Unité de Chimie des Biomolécules, URA CNRS 2128, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris cedex 15, France
An innovative strategy is described for the chemo-enzymatic synthesis of complex microbial oligosaccharides. The concept is based on the exploitation of enzyme engineering technologies to circumvent sugar organic synthesis boundaries and create new glyco-enzymes designed on purpose to enter a programmed chemo-enzymatic pathway. A semi-rational engineering approach allowed the design of α-transglucosidases with new and tremendously enhanced specificities toward non-natural protected acceptors, compatible with subsequent chemical elongation. Focused on the synthesis of serotype-specific Shigella flexneri oligosaccharide haptens, a biological model of importance for human health, glucosylation products were used at an early stage of the chemo-enzymatic pathway and evolved into building blocks serving as intermediates for the synthesis of the desired motifs. To our knowledge, this is the first report of successful engineering of α-transglucosidase acceptor specificity. Our approach demonstrates the potential of appropriate combinations of planned chemo-enzymatic pathway and enzyme engineering in glycochemistry.
Work supported by the ANR-Project OPTIGLUC 2005-2008
82
OC14
CARBOHYDRATE – LECTIN INTERACTIONS: PROBING MULTIVALENCY WITH TOPOLOGICALLY DEFINED
GLYCOCALIX[4]ARENES
Samy Cecionia,c, Sébastien Vidala*, Susan E. Matthewsb, Anne Imbertyc* and Jean-Pierre Pralya
(a) ICBMS/Laboratoire de Chimie Organique 2–Glycochimie/UMR 5246, Université Claude Bernard
Lyon 1, CNRS, 43 Blvd du 11 Novembre 1918, F-69622 Villeurbanne, France (b) School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK
(c) CERMAV – CNRS/UPR 5301, 601 rue de la chimie, BP 53, F-38041 Grenoble, France * [email protected] * [email protected]
The fundamental study of glycomics is now recognized as a challenge of prime importance for a better understanding of living systems.1 Many biological events are intimately linked with saccharidic structures and their interaction with lectins.2 Intercellular communication, pathogenic bacteria/virus adhesion or transmembranar signaling are some examples of these major processes. The monovalent interaction between an oligosaccharide and a protein remaining generally weak, the multivalent organization of saccharidic epitopes on cell’s surface is one of the most powerful natural tool for reaching high affinities and specificities. Mimicking Nature, the synthesis and biochemical evaluation of multivalent saccharidic structures have recently received much attention as fundamental tools for probing this concept or as potential therapeutic compounds.3
Many studies described the influence of valency or the characteristics of multivalent systems (glycodendrimers, glycopolymers, glycoclusters). In comparison, relatively few studies underlined the role of the epitopes’ 3D structural arrangement on the mechanism and/or the selectivity of interaction with lectins.
Calix[4]arenes scaffolds were used as tuneable platforms for the preparation of glycoclusters with well-defined topologies. Conjugation between these rigid scaffolds and saccharidic moieties was achieved through Cu(I)-catalyzed azide alkyne 1,3-dipolar cycloaddition.4
The resulting neoglycoconjugates were evaluated as multivalent ligands for the galactophilic lectin PA-IL5 by isothermal titration calorimetry (ITC). This lectin is suspected to play a crucial role in the adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients.
1 (a) Dwek, R. A. Chem. Rev. 1996, 96, 683-720. (b) Bertozzi, C. R.; Kiessling, L. L. Science 2001, 291, 2357-2364.
2 Mammen, M.; Choi, S.-K.; Whitesides, G. M. Angew. Chem., Int. Ed. 1998, 37, 2754-2794. 3 Gestwicki, J. E.; Cairo, C. W.; Strong, L. E.; Oetjen, K. A.; Kiessling, L. L. J. Am. Chem. Soc. 2002,
124, 14922-14933. 4 (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004-2021. (b)
Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057-3064. 5 Cioci, G.; Mitchell, E. P.; Gautier, C.; Wimmerová, M.; Sudakevitz, D.; Pérez, S.; Gilboa-Garber, N.;
Imberty, A. FEBS Lett. 2003, 555, 297-301.
83
OC15
NOVEL DI-BRANCHED MONOSACCHARIDES AND IMINO SUGARS
K. V. Booth* & G. W. J. Fleet
Department of Organic Chemistry, Chemical Research Laboratory, University of
Oxford, Mansfield Road, Oxford OX1 3TA, England; *[email protected] Molecular modelling has indicated that branched glucose analogues may be effective inhibitors of glycogen phosphorylase (GP).1 GP is involved in glycaemic response and its inhibition is one strategy under investigation against type 2 diabetes.2 With this in mind, two complementary syntheses of the di-C-methyl branched glucose analogue 5 were proposed.
The dimethyl branched lactone 2 can be synthesised in high yield from the readily available branched sugar 1,3 utilising the Kiliani reaction.4 A second Kiliani reaction gives the enantiomeric lactones 4, which are swiftly converted into the free gluco and manno configured sugars 5. Also, protection of 3 followed by treatment with Cp2TiMe2 gives 6,5 which after dihydroxylation and deprotection affords 3,5-di-C-methyl-L-fructose 7 (Scheme 1). It has been demonstrated that many sugars may be interconverted via enzymatic pathways.6 Therefore, we envisage that treatment of a branched sugar, such as 7, in a similar fashion will give the desired 3,5-di-C-methyl-L-glucose and/or mannose 5 in a single step. This is currently under investigation.
Scheme 1: Divergent syntheses of branched sugars from novel lactone 2.
Imino sugars, in which the endocyclic oxygen has been replaced by nitrogen, have shown potential as therapeutics for lysosomal storage disorders, provoking exploration into the synthesis of branched analogues.7 By introduction of an azide functionality, lactone 2 has been used in the synthesis of 9, a branched hydroxy proline derivative (Scheme 1). 1 Martin, J. L., PhD thesis, 1989, Oxford University. 2 Sher, P. M., et. al. U.S. Pat. Appl., 2005, US 7,365,061 B2. 3 Booth, K. V., et. al. Tetrahedron: Asymm., 2008, doi:10.1016/j.tetasy.2008.10.013. 4 Hotchkiss, D. J., et. al. Tetrahedron Lett., 2004, 45, 9461-9464. 5 Petasis, N. A., Bzowej, E. I. , J. Am. Chem. Soc., 1990, 112, 6392-6394. 6 Jones, N. A., et. al. Tetrahedron: Asymm., 2008, 19, 1904-1918. 7 Asano, N., Glycobiology, 2003, 13, 93-104.
84
OC16
SYNTHETIC APPROACHES TO NOVEL THIOSUGAR SCAFFOLDS CONTAINING αααα,ββββ-UNSATURATED CARBONYL FUNCTIONS
Nuno M. Xavier* and Amélia P. Rauter
Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências da
Universidade de Lisboa, Ed. C8, 5º Piso, Campo Grande, P-1749-016 Lisboa, Portugal; [email protected]
Thiosugars which comprise a sulfur atom in the ring, possess interesting chemical and biological properties and have gained importance in glycobiology and in drug design, namely as glycosidase inhibitors or as potential anticancer and anti HIV agents.1,2 Moreover sugar-derived unsaturated carbonyl compounds, such as lactones or ketones, possess inherent biological activity and are building blocks of high synthetic versatility, both owing to their electrophilic conjugated functionality.3 Linking thiosugar units to α,β-unsaturated carbonyl systems may therefore provide potential bioactive compounds and also useful scaffolds for the synthesis of new thiosugar derivatives. With the aforementioned motivations in mind and based on our previous approaches to sugar-derived butenolides,4,5 we have turned our attention towards new thiosugar targets, namely those containing α,β-unsaturated lactones (compounds type 1 and 2) and ketones (compounds type 3). For their synthesis, we employed furan-3-uloses as starting materials and we based our methodologies on intermolecular cyclization approaches, taking advantage of the ability of the free sugar ring to undergo furanose-pyranose interconversion. In this communication we will present the synthetic routes and discuss our results for the preparation of these functionalized new thiosugars.
S
O
ROS
RO
O
O
SRO
O
O1 2 3
Acnowledgments: N.M. Xavier thanks Fundação para a Ciência e Tecnologia for a PhD grant.
1 Robina, I.; Vogel, P.; Witczak, Z. J. Curr.Org. Chem. 2001, 5, 11771214. 2 Witczak, Z. J.; Culhane, J. M. Appl. Microbiol. Biotechnol. 2005, 69, 237–244. 3 Xavier, N. M., Rauter, A. P. Carbohydr. Res. 2008, 343, 15231539 4 Xavier, N. M.; Rauter, A. P. Org. Lett. 2007, 9, 33393341. 5 Xavier, N. M.; Silva, S.; Madeira, P. J. A.; Florêncio, M. H.; Silva, F. V. M.; Justino, J.; Thiem, J.;
Rauter, A. P. Eur. J. Org. Chem. 2008; in press
85
P1
CONVERSION OF KETOHEXOSES INTO HETEROBICYCLIC GLYCO-HYBRIDS
Ana C. Simão*,a,b Arnaud Tatibouët,a Amélia P. Rauter,b and Patrick Rollina
(a) ICOA – UMR 6005, Université d‘Orléans, BP 6759, F-45067 Orléans, France (b) Carbohydrate Chemistry Group, Centro de Química e Bioquímica/Departamento de Química e
Bioquímica, Faculdade de Ciências da Universidade de Lisboa – Campo Grande, Edifício C8, 5ºPiso, 1749-016 Lisboa, Portugal
[email protected] Carbohydrates are one of the most abundant classes of biomolecules, which represent about 200 billions of tons of renewable biomass - only 3% of it being used by man. Even though a great deal of efforts has been made in recent years with a view of boosting the use of inexpensive carbohydrates as raw materials, a long way still remains to be covered. Whereas conversion procedures of fossile raw materials into a wide variety of products are well developed and optimized, the use of carbohydrates as raw materials would require a larger investment for research and optimization of processes. Although some ketoses like D-fructose and L-sorbose are inexpensive and accessible at a large scale, their use in industrial processes is still limited. This is mainly due to the complexity of the chemistry of ketoses, which is still poorly developed in comparison to other saccharides such as D-glucose and sucrose.1 In the present work, we disclose some recent developments in the chemistry of some ketohexose – namely D-fructose, D-psicose, D-tagatose and L-sorbose – based on the association of 1,3-oxazolidine-2-thione and 1,3-oxazolidine-2-one moieties with carbohydrate frameworks.2,3
One of our goals is to develop in fixed tautomeric forms a library of hybrid compounds to be used as probes for a better comprehension of the mechanisms of D-glucose transport (GLUT5) in relation to diabetes and obesity.4
1 F. W. Lichtenthaler Carbohydr. Res., 313, 1998, 69-89. 2 A. Tatibouët, S. Lawrence, P. Rollin, G. D. Holman, Synlett 2004, 1945. 3 A. Tatibouët, A. C. Simão, P. Rollin Lett. Org. Chem. 2005, 2, 47. 4 A. Tatibouët, J. Yang, C. Morin, G. D. Holman, Bioorg. Med. Chem. 2000, 8, 1825.
86
P2
NEW ANTIFUNGAL AND ANTIBACTERIAL COMPOUNDS: 1,3-OXAZOLINE- AND 1,3-OXAZOLIDINE-2-THIONES
FilipaV.M. Silva,a,b,c Jorge Justino,b Sandrina Silva,a,d Arnaut Tatibouët,d Patrick Rollin,d Amélia P.
Rautera*
(a) Carbohydrate Chemistry Group, Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa – Campo Grande, Edifício C8, 5ºPiso,
1749-016 Lisboa, Portugal, *[email protected] (b) Escola Superior Agrária de Santarém - IPS, Apartado 310, 2001-904, Santarém, Portugal
(c) Instituto Nacional de Recursos Biológicos, Fonte Boa, 2005-048 Vale de Santarém, Portugal (d) ICOA-UMR 6005, Université d’Olrléans, CNRS, BP6759, F-45067 Orléans Cedex 2, France
Synthesis and antimicrobial properties of twenty four compounds, which possess the structural moiety 1,3-oxazoline-2-thione (A) or 1,3-oxazolidine-2-thione (B),1 also linked or fused to sugars, will be reported.
A B
Ring construction was accomplished by reaction of compounds containing α-hydroxy carbonyl moieties with KSCN in the presence of acid.
Screening of the bioactivity is accomplished using the paper disk diffusion method.2 With respect to fungi, the pathogenic yeast Candida albicans (ATCC 10231) and the following phytopathogen filamentous fungi were used: Alternaria alternata (CBS 108.41), Biscogniauxia mediterranea (CBS 101016), Botrytis spp., Byssochlamys fulva (CBS 146.48), Colletotrichum coffeanum (CBS 396.67), Fusarium culmorum (CBS 129.73), Pyricularia oryzae (CBS 433.70), Rhizopus spp., Stachybotrys chartarum (CBS 414.95). Regarding human pathogenic bacteria, susceptibility tests were carried out with Bacillus cereus (ATCC 11778), Bacillus subtilis (ATCC 6633), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 8739), Listeria monocytogenes (ATCC 7644), Pseudomonas aeruginosa (ATCC 27853), Salmonella enteritidis (ATCC 13076) and Staphylococcus aureus (ATCC 25923). The results revealed strong antifungal and antibacterial activities of various compounds: eleven compounds were antifungal, fourteen were antibacterial and eight compounds were active against both fungi and bacteria microbes. The most potent antifungal and antibacterial compound was an oxazoline derivative which caused a potent inhibition of six fungi (inhibition diameter ∅ between 15 to 20 mm) and four bacteria (∅ between 16 to 28 mm), when compared to the inhibition diameter of the control.
1 Silva, S., Tardy, S., Routier, S., Suzenet, F., Tatibouët, A., Rauter, A.P., Rollin, P. Tetrahedron Letters 2008, 49, 5583-5586.
2 Bauer, A.W., Kirby, W.M., Sherris, J.C., Turck, M. The Am. J. Clinical Pathology 1966, 45, 493-496.
OOR NHO
S
OHor
NHO
S
KSCN, H+
87
P3
SYNTHESIS, ANTIOXIDANT AND ANTICHOLINESTERASE ACTIVITIES AND TOXICITY STUDIES OF OXO-/THIOXOPYRIMIDINE PSEUDO-C-NUCLEOSIDES
Rocio Campoy,a M. Eduarda M. Araújo,a,* Amélia P. Rauter,a Isabel Ismael,b J. M. Pinheiro,b José A.
Figueiredo,b Artur M. S. Silva,c Jorge Justino,d Filipa V. M. Silva,a,d Margarida Goularta,d
(a) Carbohydrate Chemistry Group, Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa – Campo Grande, Edifício C8, 5ºPiso,
1749-016 Lisboa, Portugal, *[email protected] (b) Departamento de Química, Unidade I&D Materiais Têxteis e Papeleiros, Universidade da Beira
Interior, Rua Marquês d’Ávila e Bolama, 6201-001 Covilhã, Portugal (c) Departamento de Química, Universidade de Aveiro, Campus Universitário de Santiago,
3810-193 Aveiro, Portugal (d) Escola Superior Agrária de Santarém, Instituto Politécnico de Santarém, Apartado 310,
2001-904 Santarém, Portugal Radical oxygen species (ROS) are reactive chemical entities which, when over-produced by endogenous or external sources, lead to oxidative stress, which is related to many diseases such as cancer, arteriosclerosis and cardiovascular problems, neurodegenerative lesions, diabete and even ageing.
In this work, the β-carotene-linoleate bleaching assay1 was used to evaluate the antioxidant activity of three pseudo-C-nucleosides, namely the thioxopyrimidine derivatives 1, 2 and the oxopyrimidine C-nucleoside 3. Their synthesis was accomplished in high yield by reaction of the sugar aldehyde precursors with ethyl acetoacetate and urea or thiourea, under conventional heating (5 h) or alternatively using microwave irradiation at 300W (10 min).
The antioxidant activity was evaluated and the results are shown in Table 1. We determined the IC50 for β-carotene bleaching based on the absolute change in absorbance against a water control after 2 h reaction, as well as the percent inhibition of the β-carotene bleaching (% ANT) and the oxidation rate ratio (ORR) relative to the aqueous control.1 For the last two procedures, the concentration of the test substances was 0.1 mg mL-1 and the reaction was followed for 50 min.
Table 1 – Antioxidant activity of compounds 1-3 compound IC50 (mg.mL-1) %ANT ORR
1 0.103±0.001 80 0.2 2 0.130±0.037 80 0.2 3 0.884±0.077 33 0.7
The studied compounds inhibited acetylcholinesterase (26 - 44% inhibition at 100 µg/mL), an enzyme involved in the neurotransmission in the brain, indicating that these compounds may be of potential interest for the control of Alzheimer’s disease. No cytoxicity nor genotoxicity was detected for the bioactive compounds with the galactose protected moiety at relevant bioactive concentrations. 1 Amarowicz, R., Pegg, R.B., Rahimi-Moghaddam, P., Barl, B., Weil J.A., Food Chemistry 2004, 84,
551-562.
OBn
HN
HNS CH3
CO2Et
O
O
O
1
HN
HNX CH3
CO2Et
2: X=S3: X=O
O
OO
O
O
88
P4
CYTOTOXIC ACTIVITY OF SUGAR-DERIVED αααα,ββββ-UNSATURATED CARBONYL COMPOUNDS
Catarina Sepúlveda,* Margarida Meireles, Nuno M. Xavier, Amélia P. Rauter
Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências da
Universidade de Lisboa – Campo Grande, Edifício C8, 5ºPiso, 1749-016 Lisboa, Portugal, *[email protected]
α,β-Unsaturated carbonyl compounds, notably lactones and ketones, are known to possess a broad variety of biological and pharmacological activities such as cytotoxic and antitumour.1 Their ability to act as Michael acceptors for the addition of enzymes’ nucleophiles, specially sulfydryl groups is supposed to play a key role in determining bioactivity.2 In particular, sugars containing such system have attracted much attention not only due to their potential biological profile but also for their use as precursors for the synthesis of many bioactive compounds.3 In this context, we decided to study the cytotoxic activity of some of our recently synthesised sugar-based butenolides (compounds type 1-3) and α,β-unsaturated esters (compounds of type 4).4,5,6
Formation of the lactone moieties in type 1 compounds was accomplished by reaction of the epoxide precursor with the di-anion of phenylselenoacetic acid, followed by acid-catalysed oxidation and elimination.4 The methodology for the preparation of compounds of types 2 and 3 was based on the stereoselective Wittig olefination of 5-keto and 3-keto sugars, respectively, and subsequent intramolecular lactonization of the intermediate γ-hydroxy- α,β-unsaturated esters.5,6 Sugar-derived α,β-unsaturated esters 4, intermediates for the synthesis of the bicyclic fused-derivatives 3, were also included in our set of compounds.
The antiproliferative effect of these new targets was evaluated in vitro, using the MTT colorimetric method, against HeLa cervix carcinoma cell line and expressed as IC50 values. Among the series, three compounds exhibited interesting growth inhibitory effects. These results will be disclosed and correlated with the structural features of the compounds tested.
O
O
O
RO
O
OO
OO
O
RO OO
O
O
1 2 3
O
OO
HCCO2Et
R1O
R2O
4
RO
1 Cateni, F.; Zilic, J.; Zacchigna, M.; Bonivento, P.; Frausin, F.; Scarcia, V. Eur. J. Med. Chem. 2006,
41, 192–200. 2 Favier, L. S.; Maria, A. O. M.; Wendel, G. H.; Borkowski, E. J.; Giordano, O. S.; Pelzer, L.; Tonn, C.
E. J. Ethnopharmacol. 2005, 100, 260–267. 3 Xavier, N. M., Rauter, A. P. Carbohydr. Res. 2008, 343, 1523−1539. 4 Rauter, A. P.; Figueiredo, J. A.; Ismael, M.; Canda, T.; Font, J.; Figueredo, M. Tetrahedron:
Asymmetry 2001, 12, 1131−1146. 5 Xavier, N. M.; Rauter, A. P. Org. Lett. 2007, 9, 3339−3341. 6 Xavier, N. M.; Silva, S.; Madeira, P. J. A.; Florêncio, M. H.; Silva, F. V. M.; Justino, J.; Thiem, J.;
Rauter, A. P. Eur. J. Org. Chem. 2008, 6134−6143.
89
P5
MASS SPECTROMETRY STUDY OF SUGAR-FUSED BUTENOLIDES
Paulo J. A. Madeira,* Ana M. T. G. Rosa, Nuno M. Xavier, Amélia P. Rauter, M. Helena Florêncio
Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências da
Universidade de Lisboa, Edifício C8, 5o Piso, Campo Grande, 1749-016 Lisboa, Portugal *[email protected]
Fragmentation pathways of five-membered ring lactones using electrospray ionization tandem mass spectrometry have been reported.1 The fragmentation mechanisms of these lactones and their behaviour can be extended to larger and more complex natural products. α,β-Unsaturated γ-lactones show a variety of biological properties including antifungal2 and insecticidal3 activities due to their structural feature and little is known about the gas-phase behaviour of these compounds. Therefore, a mass spectrometry study of a series of newly synthesized sugar-fused butenolides4 (Figure 1) was carried out.
Figure 1: Structures of the sugar-fused butenolides under study.
The behaviour of compounds 1-5 using Electrospray Ionization and Tandem Mass Spectrometry is presented and discussed in order to establish the fragmentation mechanisms of these molecules.
Acknowledgments: The authors P.J.A.M. and N.M.X. acknowledge the FCT for the PhD grants (SFRH/BD/27614/2006 and SFRH/BD/39251/2007 respectively). 1 Crotti A. E. M. et al. Int. J. Mass Spectrom. 2004, 232, 271-276. 2 Justino J. et al. Pest Manag. Sci. 2005, 61, 985-990. 3 Rauter, A. P. et al. Tetrahedron: Asymmetry 2001, 12, 1131-1146. 4 Xavier, N. M. et al. Eur. J. Org. Chem. 2008, 6134-6143.
90
P6
PURINE NUCLEOSIDES AS NEW AGENTS FOR THE CONTROL OF ALZHEIMER’S DISEASE
Filipa V.M. Silva,a,b Filipa Marcelo,a,c Jorge Justino,b Ana P. Jacob,b Yves Blériot,c Pierre Sinaÿ,c
Margarida Goulart,d Amélia P. Rautera,*
(a) Carbohydrate Chemistry Group, Centro de Química e Bioquímica / Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Edifício C8, 5º Piso, 1749-016, Lisboa, Portugal, *[email protected]
(b) Escola Superior Agrária de Santarém do Instituto Politécnico, Quinta do Galinheiro, Apartado 310, 2001-904, Santarém, Portugal
(c) Équipe de Glycochimie Organique, Biologique et Supramoléculaire ,UMR 7611
Université Pierre et Marie Curie, 4 Place de Jussieu, Paris, F-75005, France (d)Instituto Tecnológico e Nuclear, Unidade de Protecção e Segurança Radiológica,
E.N.10, Apartado 21, 2686-953 Sacavém, Portugal
Synthesis of novel and unusual purine nucleosides (compounds type A) was carried out starting from the 1-acetoxy glycosyl donors and 2-acetamido-6-chloropurine promoted by TMSOTf.The potential of these nucleosides and their sugar precursors as agents to control Alzheimer’s disease (AD) was investigated. Presently, some of the approved drugs for AD therapeutics are inhibitors of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), being those enzymes involved in the neurotransmission. Thus, inhibition of bovine AChE and human BChE by these compounds and precursors, at concentrations ranging between 0.01 and 100 µg/mL, was assessed. The concentrations required for 50% enzyme inhibition (IC50) were estimated for the active substances. Moreover, direct cytotoxicity of the active compounds at final concentration of 2500 µg/mL was assessed in vitro by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method.
Most of the compounds tested inhibited BChE, although no inhibition was observed for AChE. N7-Nucleosides were the most promising compounds since significant BChE inhibitions were registered at the concentration of 100 ng/mL (IC50 values 0.12-0.55 µg/mL or 0.14-0.76 µM). Those IC50 values were comparable to the results obtained for standard approved drugs currently in use to treat Alzheimer patients (IC50 values 0.069-1.1 µg/mL or 0.17-2.7 µM). Thus, regioselectivity towards N7 glycosylation was accomplished by tuning the reaction conditions. Remarkably, some of the nucleobase-free bicyclic compounds were still very active against BChE (IC50 values 2.8-10.3 µg/mL or 4.2-16.1 µM). Low values for cytotoxicity and genotoxicity were obtained and encourage further investigation of these compounds for the control of neurodegenerative disorders such as Alzheimer’s disease.
91
P7
PRACTICAL CONVERSION OF SUGARS INTO HYDROPHILIC N-HETEROCYCLES
Eckehard Cuny, Frieder W. Lichtenthaler
Institut für Organische Chemie, Technische Universität Darmstadt,
64287 Darmstadt, Germany, *[email protected]
To improve the competitiveness of low molecular weight carbohydrates over petrochemical raw materials, the development of practical, large-scale adaptable reaction channels is required leading from cheap, ton-scale accessible sugars to building blocks with industrial application profiles.1 Reaction channels that have not been exploited systematically, are the conversion of sugars into N-heterocycles − a transformation which occurs extensively on exposure of foodstuffs to heat, yet straightforward preparative procedures are deficient. We here present the elaboration of two preparatively satisfactory reaction sequences leading from ton-scale accessible, inexpensive sugars to variably functionalized hydrophilic imidazoles, pyrazoles, pyrroles, pyridines, pyridazines, quinoxalines, and benzodiazepines.2,3 Imidazoles of type 1 can be generated in a one-step synthesis by cyclization of reducing sugars with formamidine acetate in a melt of ammonium carbonate (yields >50%). Another one-pot reaction involves exposure to phenylenediamine in aqueous hydrazine, providing quinoxalines of type 2 (>60%).
a. R1=R2=H b. R1=α-D-Glc, R2=H c. R1=H, R2=α-D-Glc, d. R1=H, R2=β-D-Gal, e. R1=H, R2=β-D-Glc
R1O
HO HO
N
N
OR2
H2N
H2N
N2H4/H
2
a. D-Glucoseb. Isomaltulosec. Maltosed. Lactosee. Cellobiose
1
(NH4)2CO3
R1O
OHOH
NHNOR2 NH
NH2H
Conversion of D-fructose or isomaltulose into pyrroles, pyridazines, and benzodiazepines of type 5-7 is readily accomplished by acidic dehydration, subsequent oxidative opening of the furan ring to the corresponding 1,4-dicarbonyl compounds (→ 3, 4), and concluding cyclization with amines or hydrazine.
o-C6H4(NH2)2 1. TiCl32. NH3
2. O2, hν
1. H2O, H
3. MCPBA
1. H2O, H2. NaBH4
H
HN
N
O
RO O
N N OHRONOH
HRO
D-Fructose Isomaltulose
N2H4
R = H R = α-D-Glc
RO O OOH
3 4
5 6 7
OHORO O
1 Lichtenthaler, F. W. “Carbohydrates as Renewable Raw Materials: A Major Challenge of Green
Chemistry”, Methods and Reagents for Green Chemistry (P. Tundo, A. Perosa, Eds.) J. Wiley, Hoboken, NJ, 2007, pp. 23-63.
2 Brust, A., Cuny, E., Lichtenthaler, F. W. Green Chemistry 2001, 201-209. 3 Lichtenthaler, F. W. “Unsaturated O- and N-Heterocycles from Carbohydrate Feedstocks“, Acc.
Chem. Res. 2002, 35, 728-737.
92
P8
BIOACTIVE COMPOUNDS DERIVED FROM FRUCTOSE
Ana Catarina Araújo,a* Amélia P. Rauter,a Rossella Zoboli,b Cristina Airoldi,b Barbara Costa,b Laura Cipollab and Francesco Nicotraa
(a) Carbohydrate Chemistry Group, Centro de Química e Bioquímica/Departamento de Química e
Bioquímica, Faculdade de Ciências da Universidade de Lisboa – Campo Grande, Edifício C8, 5ºPiso, 1749-016 Lisboa, Portugal, * [email protected]
(b) Dipartimento di Biotecnologie e Bioscienze, Università di Milano – Bicocca, Piazza della Scienza 2, 20126 Milano, Italia.
GABAA receptors are the major inhibitory neurotransmitter receptors. They are chloride ion channels activated by the binding of the neurotransmitter γ-aminobutyric acid (GABA).1 GABAA receptors are not only pivotal for normal brain function but they are also relevant drug targets.2
The GABAA receptor complex consists of a large number of binding sites for drugs, notably benzodiazepines, neurosteroids, and barbiturates. Consequently, compounds that act at GABA receptors have considerable therapeutic interest for use in a variety of neurological disorders. In this context we used fructose as the scaffold for the synthesis of different compounds as potential GABAA ligands, directed at the GABA (compounds 1-6)3 or benzodiazepine binding site (compounds 7-22)4 respectively, Fig. 1. Carbohydrates are often exploited as chiral scaffolds with pharmaceutical and medical applications.5 It has been observed that carbohydrate containing drugs present very often interesting pharmacokinetic properties, that can be tuned by partial derivatisation of the hydroxyl groups with lipophylic appendages. The fructose moiety acts as versatile scaffold, being rich in stereochemistry and having a relatively rigid skeleton. For GABA receptor ligand action, penetration of the blood-brain barrier (BBB) is required, and lipophilicity is the most important parameter that crucially influences its penetration.
All compounds were characterized in receptor binding studies at GABAA receptors using rat brain membrane preparations.
Fig. 1. Structure of the fructose-based GABAA receptor ligands
1 Stephenson, F.A. Biochem. Soc. Trans., 2006, 34, 877. 2 Krogsgaard-Larsen, P., Frølund, B., Liljefors, T. Chem. Record, 2002, 2, 419. 3 Araújo, A. C., Nicotra, F., Costa, B., Giagnoni, G., Cipolla, L. Carbohydr. Res., 2008, 343, 1840. 4 Araújo, A.C., Nicotra, F., Airoldi, C., Costa, B., Giagnoni, G., Fumagalli, P., Cipolla, L. Eur. J. Org., 2008, 635. 5 Hanessian, S. In Total Synthesis of Natural Products: The “Chiron” Approach; Baldwin, J. E. Ed., Pergamon: Oxford, 1983.
O
RO
ROOR
O
O
1: R = Bn2: R = H
O
RO
ROOR
N
O
R1
3: R = Bn, R1 = CO2tBu4: R = Bn, R1 = H5: R = H, R1 = CO2tBu6: R = R1 = H
N
N
O
R1
X
OH
O
R2OR2O
R2O
7a/7b: R1 = H, X = H, R2 = Bn8a/8b: R1 = CH3, X = H, R2 = Bn9a/9b: R1 = H, X = NO2, R2 = Bn10a/10b: R1 = CH3, X = NO2, R2 = Bn11a/11b: R1 = H, X = Br, R2 = Bn12a/12b: R1 = CH3, X = Br, R2 = Bn13a/13b: R1 = H, X = Cl, R2 = Bn14a/14b: R1 = CH3, X = Cl, R2 = Bn
N
N
O
R1
X
OH
O
R2O
R2O
R2O
15a/15b: R1 = H, X = H, R2 = H16a/16b: R1 = CH3, X = H, R2 = H17a/17b: R1 = H, X = NH2, R2 = H18a/18b: R1 = CH3, X = NH2, R2 = H19a/19b: R1 = H, X = Br, R2 = H20a/20b: R1 = CH3, X = Br, R2 = H21a/21b: R1 = H, X = Cl, R2 = H22a/22b: R1 = CH3, X = Cl, R2 = H
7a-22a 7b-22b
93
P9
THE UTILITY OF THE BENZHYDRYL PROTECTING GROUP IN THE SYNTHESIS OF IMINOSUGARS
S. F. Jenkinson,a R. J. Newell,a T. B. Mercer,a R. Higham,a S. D. Rule,a D. Best,a* A. C. Weymouth-
Wilson,b S. Petursson,c G.W.J. Fleeta
(a) Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
*[email protected] (b) Dextra Laboratories Limited, The Science and Technology Centre, Whiteknights Road, Reading,
RG6 6BZ, UK (c) Faculty of Business and Science, University of Akureyi, IS-600 Akureyi, Iceland;
Iminosugars are an important class of glycosidase inhibitors and therefore have potential as mechanistic probes and therapeutic agents for numerous diseases.1 In order to design short efficient syntheses of iminosugars a good protection strategy is required to avoid protecting group migration, common with silyl ethers and acetyl groups, and epimerisation, often occurring with the use of benzyl ethers. The benzhydryl (diphenylmethyl) group can be introduced in high yield under neutral conditions to protect hydroxyl groups of sugar lactones that are prone to base catalyzed epimerisation and/or elimination.2 In addition the protection of highly hindered alcohols can readily be achieved. The utility of the benzhydryl protecting group has been demonstrated by the synthesis of several polyhydroxylated piperidines and pyrrolidines in short high yielding sequences. No migration or epimerisation at C-2 was observed.
O
OO
OBzh
OBnN
OO
OBzh
RN
OHHOOH
L-Arabinose
O
OO
Ph
OBzh
ORN
OHHOOH
BnN
OO
Ph
OBzhD-Ribose
O
O O
BzhOO
BnN
O O
BzhO
RN
HO OH
HO
RN
HO OH
HO
D-lyxonolactone
D-xylose
RN
HO OH
HO
RN
HO OH
HO
RN
HO OH
HOOH
BnN
BzhOOBzh
O O
OBzhO
OBzh
O
O O
O
O O
BzhOO
BnN
O O
BzhO
O
O O
BzhOO
BnN
O O
BzhO
O
O O
BzhOO
BnN
O O
BzhO
R = Bn, H
1 Watson, A. A., Fleet, G. W. J., Asano, N., Molyneux, R. J., Nash, R. J. Phytochemistry 2001, 56,
265-295. 2 Best, D., Jenkinson, S .F., Rule, S. D., Higham, R., Mercer, T. B., Newell, R. J., Weymouth-Wilson,
A., Fleet, G. W. J., Petursson, S. Tetrahedron Lett. 2008, 49, 2196-2199.
94
P10
SYNTHESIS OF 3-FLUORO OXETANE δδδδ-AMINO ACIDS
Susana D. Lucas,a,* Amélia P. Rauter,a Hans P. Wesselb
(a) Carbohydrate Chemistry Group, Centro de Química e Bioquímica/Departamento de Química e
Bioquímica, Faculdade de Ciências da Universidade de Lisboa – Campo Grande, Edifício C8, 5ºPiso, 1749-016 Lisboa, Portugal. *[email protected]
(b) F. Hoffmann - La Roche Ltd., Pharmaceutical Research, Discovery Chemistry, CH-4070 Basel, Switzerland
Oxetane δ-amino acids 1 are useful chiral scaffolds that can be synthesized from carbohydrates.1 The four-membered rings present little flexibility and exhibit well defined exit vectors orienting the substituents in space. While pyranosidic and furanosidic carbohydrate amino acids have already shown high potential as rigid templates to induce specific conformations in peptide mimetics and to be used as scaffolds for parallel chemistry purposes, fewer contributions were made on oxetane amino acids.2
O
CO2H
R
BocHN
1
O
F
OBocHN
OH
2
O
FOH
OBocHN
3
Figure 1
In the present work we report the synthesis of oxetane δ-amino acids with different configurations and containing a fluoride substituent at C-3. It has been well recognised that the presence of fluorine can induce favourable properties in bioactive compounds.3 Starting from D-xylose, the 3-fluoro-D-arabinonic acid 2 was synthesized over 10 steps. For the synthesis of the analogous D-xylo derivative the starting material was 1,2-O-isopropylidene-α-D-xylofuranose, and a total of 14 steps led to the desired compound 3.
Acknowledgments: SDL thanks Fundação para a Ciência e Tecnologia for a PhD grant.
1 (a) Johnson, S. W., Jenkinson (née Barker), S. F., Angus, D., Jones, J. H., Watkin, D. J., Fleet, G.
W. J. Tetrahedron Asymm 2004, 15, 3263–3273. (b) Lucas, S.D., Iding, H., Alker, A., Wessel, H.P, Rauter, A.P. J. Carbohydr. Chem. 2006, 25, 187-196. (c) Lucas, S.D., Rauter, A.P., Wessel, H.P., J. Carbohydr. Chem. 2008, 27, 172-187. (d) Lopez-Ortega, B., Jenkinson, S.F., Claridge, T.D.W., Fleet, G.W.J., Tetrahedron Asymmetry 2008, 19, 976-983.
2 Wessel, H.P., Lucas, S.D. Oligossacharide mimetics. In Glycoscience: Chemistry and Chemical Biology; Fraser-Reid, B.; Tatsuda, K.; Thiem, J., Eds.; Springer Verlag: Heidelberg 2008, Part 9, 2079-2112 and references therein.
3 (a) Böhm, H.-J., Banner, D., Bendels, S., Kansy, M., Kuhn, B., Müller, K., Obst-Sander, U., Stahl, M. Chem Bio Chem 2004, 5, 637-643. (b) Müller, K., Faeh, C., Diederich, F. Science 2007, 317,1881-1886.
95
P11
NEW METHODOLOGIES FOR THE SYNTHESIS OF FLUORINATED C-GLYCOSIDES
Navnath Karche, Benjamin Moreno, Florent Poulain, Eric Leclerc,* Jean-Charles Quirion
IRCOF, COBRA, UMR 6014 CNRS, Université et INSA de Rouen, 1 rue Lucien Tesnière 76130 Mont
Saint-Aignan, France, *[email protected]
The incorporation of fluorine atoms onto biomolecules or synthetic biologically active molecules has become an intense research field in the two or three past decades, especially for drug development purposes.1 This widespread interest stems from the unique properties of the fluorine atom and of the C–F bond which allow to induce alterations of crucial biological properties (such as substrate recognition, metabolic stability, drug transport,...) within limited structural modifications.1b Despite their interesting biological properties, a major drawback in the use of O-glycosides and O-glycoconjugates for drug development remains the low metabolic stability of the anomeric bond which erodes the bioavailability of carbohydrate-based drugs. It thus appeared interesting to combine the hydrolytic stability of carbohydrate analogs such as C-glycosides with the properties of fluorine to give rise to a new class of glycomimetics.2
O
OBn
OBnO
BnO
OBn
OAcO
OAcAcO
OBnO
OBnBnO
BnO
OPO
OP CF2CO2EtPO
OP
1
F
OSiMe3F
OEt
Reformatsky
BrCF2CO2EtBEt3
Glycoconjugate Mimetics
Our group aimed at providing methodologies which allowed the synthesis of CF2-glycopyranosides such as 1 from commercially available and easy-to-handle ethyl bromodifluoroacetate.3 We developed different strategies allowing the synthesis of 1 for many carbohydrate series (glucose, mannose and galactose) and for any pseudo-anomeric center configuration (α or β). This intermediate is further used as a valuable building block for the synthesis of glycoconjugate analogues.
1 (a) Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH: Weinheim, Germany, 2004. (b) Biffinger, J. C.; Kim, H. W.; DiMagno, S. G. ChemBioChem 2004, 5, 622 and references cited therein.
2 The synthesis of fluorinated C-glycosides was pioneered by William Motherwell : (a) Houlton, J. S.; Motherwell, W. B.; Ross, B. C.; Tozer, M. J.; Williams, D. J.; Slawin, A. M. Z. Tetrahedron 1993, 49, 8087. (b) Herpin, T. F.; Motherwell, W. B.; Weibel, J.-M. Chem. Commun. 1997, 923.
3 (a) Karche, N. P.; Pierry, C.; Poulain, F.; Oulyadi, H.; Leclerc, E.; Pannecoucke, X.; Quirion, J.-C. Synlett 2007, 123. (b) Moreno, B.; Quehen, C.; Rose-Hélène, M.; Leclerc, E.; Quirion, J.-C. Org. Lett. 2007, 9, 2477. (c) Poulain, F.; Serre, A.-L.; Lalot, J.; Leclerc, E.; Quirion, J.-C. J. Org. Chem. 2008, 73, 2435.
96
P12
TRANSFORMATION OF PARTIALLY UNPROTECTED THIOGLYCOSIDES AND n-PENTENYL GLYCOSIDES INTO GLYCOSYL FLUORIDES MEDIATED BY
NIS/HF-PYRIDINE
Paloma Bernal-Albert, Clara Uriel, Ana M. Gómez, Juan Ventura, J. Cristóbal López*
Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
We have described recently the use of bis(pyridinium) iodonium (I) tetrafluoroborate (IPy2BF4)
1 for the conversion of partially unprotected thioglycosides and n-pentenyl glycosides into their orthogonal partners glycosyl fluorides.2,3 In this transformation, IPy2BF4
functionned as a synthetic equivalent of iodine monofluoride, thus being a source of electrophilic iodonium ion that activates the anomeric leaving group, and nucleophilic fluoride that reacts with the anomeric oxo-carbenium ion. Even though IPy2BF4 is a commercially available, crystalline reagent, we have sought for more accessible alternatives. Herein we disclose that N-iodosuccinimide (NIS), N-bromosuccinimide (NBS), or iodonium dicollidinium perchlorate (IDCP), can be employed in the presence of HF-pyridine, in the transformation of partially unprotected thioglycosides and n-pentenyl glycosides into glycosyl fluorides (Scheme 1).
1 (a) Barluenga, J.; Campos, P. J.; González, J. M.; Suárez, J. L. J. Org. Chem. 1991, 56, 2234–2237. (b) Barluenga, J. Pure Appl. Chem. 1999, 71, 431–436. 2 López, J. C.; Uriel, C.; Guillamón-Martín, A.; Valverde, S.; Gómez, A. M. Org. Lett. 2007, 9, 2759-
2762 3 López J. C.; Bernal-Albert, P.; Uriel, C.; Valverde, S.; Gómez, A. M. J. Org. Chem. 2007, 72, 1387–
1395
97
P13
SYNTHESIS OF gem-DIFLUOROCARBASUGARS AND RELATED PSEUDO-CARBASUGARS
João Sardinha,a,b,* Amélia P. Rauter,b Pierre Sinaÿ,a Matthieu Sollogouba
(a) Université Pierre et Marie Curie – Paris 6, Institut de Chimie Moleculaire (FR 2769), Laboratoire de
Chimie Organique (UMR CNRS 7611), Glycochimie Organique Biologique et Supramoléculaire (b) Carbohydrate Chemistry Group, Centro de Química e Bioquímica/Departamento de Química e
Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Edíficio C8, 5º Piso, 1749-016 Lisboa, Portugal.*[email protected]
The synthesis of sugar analogues is an important domain in glycochemistry that has led to the development of drugs such as Glucobay™, Zavesca™ or Tamiflu™. Carbasugars are sugar analogues in which the endocyclic oxygen atom is replaced by a methylene group. They have attracted attention as hydrolytically stable mimetics of their parent sugars. Such molecules have been helpful, for instance, for the elucidation of biosynthetic mechanisms. However, the effectiveness of carbasugars as sugar mimetics is compromised by electronic effects associated with the replacement of the oxygen by a methylene group. To overcome this disadvantage, we envisaged the synthesis of gem-difluorocarbasugars which may act as closer sugar mimetics, due to the electronegative properties of the fluorine atom.
The synthetic strategy is based on a rearrangement, induced by a Lewis acid, of a functionalized sugar containing a cobalt-cluster and an enol ether moiety.
This approach has been applied successfully to the glucose,1 galactose and mannose series.2 In addition, synthesis of the 5-fluoro-(+)-MK7607 and its 1-epimer,3 compounds regarded as pseudo-carbasugars, will be presented and discussed. The (+)-MK7607 is a patented naturally occurring unsaturated pseudo-carbasugar possessing herbicidal activity.
1 Deleuze, A.; Menozzi, C.; Sollogoub, M.; Sinaÿ, P. Angew. Chem. Int. Ed Engl. 2004, 43, 6680-6683. 2 Sardinha, J.; Guieu, S.; Deleuze, A.; Fernández-Alonso, M. C.; Pilar Rauter, A.; Sinaÿ, P.; Jiménez-
Barbero, J.; Sollogoub, M. Carbohydr. Res. 2007, 342, 1689 – 1703. 3 Sardinha J.; Rauter A. P.; Sollogoub M., Tetrahedron Lett. 2008, 49, 5548-5550.
98
P14
1,2 DIFUNCTIONAL SYSTEMS FROM BICYCLIC CARBOHYDRATE LACTONES
Y. Queneau,a,b,* R. Cheaib,a,b N. M. Xavier,c A. Listkowski,a,b S. Chambert,a,b A. P. Rauterc
(a) INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne.
(b) CNRS, UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université Lyon 1 ; INSA Lyon ; CPE Lyon. *[email protected]
(c) Carbohydrate Chemistry Group, Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa – Campo Grande, Edifício C8, 5ºPiso,
1749-016 Lisboa, Portugal
Carboxymethylglycoside lactones (CMGL) are synthons which are readily available in 2 or 3 steps from unprotected carbohydrates by simple procedures. By reaction with nucleophilic species, notably amines, various types of carbohydrate-containing compounds, such as surfactants or pseudo glycoconjugates.1 A free hydroxyl group being present at position 2 after the lactone opening reaction, bisfunctionalized systems can easily be obtained.2 We report herein the study of various transformations at C-2 and OH-2 of the adducts. Notably, within the context of our research program dedicated to the synthesis of biologically active carbohydrate-based unsaturated carbonyl systems, notably lactones,3 new α,β-unsaturated ketones were obtained by oxidation of OH-2 to form the 2-ulose analogs, followed by 3,4-elimination. The outcome of this last step proved to depend on the configurations at C-1 and C-4 and on the type of substituents at positions 3, 4 and 6.
O
ORO
OH
ORO
O
O
CO2H
HO
OHOHO
HO
OH
O O
OH
OH OH
OHBrCH2CO2tBu, base (R = Ac) H2O2, WO4, H+ (α only)
RuCl3-NaIO4 or O3
b
c
a
O
O O
O
HOO
O
O
O
OO
O
isomaltulose
CMG
CMGL
O
OO
O
RO
RO
RO
OR
1 Pierre, R., Chambert, S., Alirachedi, F., Danel, M., Trombotto, S., Doutheau, A., Queneau, Y. C. R.
Chimie, 2008, 11, 61-66; Trombotto, S., Danel, M., Fitremann, J., Bouchu, A., Queneau., Y. J. Org. Chem., 2003, 68, 6672-6678; Le Chevalier, A., Pierre, R., Chambert, S., Doutheau, A., Queneau., Y. Tetrahedron Lett., 2006, 47, 2431-2434; Chambert, S., Cowling, S. J., Mackenzie, G., Goodby, J. W., Doutheau, A., Queneau Y. J. Carbohydr. Chem., 2007, 26, 27-39; Listkowski, A., Ing, P., Cheaib, R., Chambert, S., Doutheau, A., Queneau, Y. Tetrahedron: Asymmetry, 2007, 18, 2201-2210.
2 Cheaib, R. Listkowski, A., Chambert, S. Queneau, Y. Tetrahedron: Asymmetry, 2008, 19, 1919-1933.
3 Rauter, A. P.; Figueiredo, J. A.; Ismael, M.; Canda, T. ; Font J. ; Figueredo, M. Tetrahedron: Asymmetry, 2001, 12, 1131-1146; Justino, J. ; Rauter, A. P. ; Canda, T. ; Wilkins R. ; Matthews, E. Pest Manag. Sci., 2005, 61, 985-990.
99
P15
SYNTHESIS OF NOVEL ALKYL GLYCOSIDES AS POTENTIAL INHIBITORS/SUBSTRATES FOR MYCOBACTERIAL
GLYCOSYLTRANSFERASES
M. Poláková,a* M. Beláňová,b K. Mikušová,b and L. Petruša
(a) Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 38 Bratislava, Slovakia, *[email protected]
(b) Comenius University, Faculty of Natural Sciences, Department of Biochemistry, SK-842 15, Bratislava, Slovakia
Mycobacterial diseases, such as tuberculosis, represent a serious worldwide problem. A morphologic feature common to all mycobacteria is their complex cell wall, which is made up of polysaccharides, proteins and lipids. Arabinogalactan and lipoarabinomannanan, which are major polysaccharide components of the mycobacterial cell wall, contain three kinds of sugar units - mannopyranose, galactofuranose and arabinofuranose in a variety of defined glycosidic linkages.1
Chemistry of carbohydrates mimics is a dynamic area, since such compounds have shown interesting biological properties. Carbohydrate mimics have been synthesized and screened as potential substrates/inhibitors of mycobacterial glycosyltransferases as well.2
Our goal was to accomplish synthesis of selected mimics containing mannopyranose and arabinofuranose units. Several glycosylation methods, using different promoters were investigated in order to obtain series of novel glycosides; e.g.; those with various length of alkyl chain, S-glycosides and sulphones. Selected glycosides were further modified and their conjugates were obtained by click chemistry and olefin metathesis.
Potential inhibitory effects of the prepared compounds on the activity of the selected mycobacterial glycosyltransferases, as well as their capacity to serve as their substrates, were tested using in vitro assays. The results will be discussed.
Acknowledgements: This work was supported by the APVV-51-046505, VEGA-2/6129/27 grants, and by European Comission under contract LSHP-CT-2005-018923“NM4TB“.
1 Chatterjee, D., Khoo, K.-H. Glycobiology 1998, 8, 113-120. 2 Tam, P.-H., Besra, G.S., Lowary, T.L. ChemBioChem 2008, 9, 267-278.
Pathak, A.K., Pathak V., Maddry, J.A., Suling W.J., Gurcha S.S., Besra, G.S., Reynolds, R.C. Bioorg. Med. Chem. 2001, 9, 3145-3151. Subramaniam, V., Gurcha, S.S., Besra G.S., Lowary, T.L. Biorg. Med. Chem. 2005, 13, 1083-1094.
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P16
SYNTHESIS OF CYTOTOXIC GLYCOSYLATED DERIVATIVES OF OXYSTEROLS
João F. S. Carvalho,a* M. Manuel Cruz Silva,a Sérgio Simões,b Sergio Riva,c M. Luísa Sá e Meloa
(a) Centro de Estudos Farmacêuticos, Lab. Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Rua do Norte 3000-295, Coimbra, Portugal, * [email protected]
(b) Centro de Neurociências e Biologia Celular, Grupo de Terapia Génica, Universidade de Coimbra, 3000-295 Coimbra, Portugal
(c) Istituto di Chimica del Riconoscimento Molecolare, C.N.R., Via Mario Bianco 9, 20131 Milano, Italy
Carbohydrates play an important role in drug discovery and special emphasis can be placed for the development of pharmaceutically active compounds. The presence of a sugar moiety in a molecule can dramatically affect its physical, chemical and biological properties1. Pharmacokinetics of glycosylated drugs is significantly different due to its higher polarity. Moreover drug interaction with receptors can be affected, leading to changes in the biological properties. Actually, research on the biological and pharmacological role of sugar moieties is still deserved. In most cases the sugar itself is not active, as was demonstrated for many antibiotics and antitumor compounds, being erythromycin, daunomycin or amphotericin B important examples. Therefore, in vitro studies comparing biological activities of drugs and their glycosyl derivatives are helpful to understand the effect of the glycosyl moieties in the overall drug activity. Our group has developed a systematic study on the cytotoxicity of a library of oxysterols, i.e. in oxygenated derivatives of cholesterol. Oxysterols have gained increasing attention in Medicinal Chemistry due to their wide range of biological effects2, such as cytotoxic activity in tumoral cell lines. Steroidal glycosides, saponins, have been isolated from a wide variety of both plant and animal sources3 and have interesting effects on animals4. Some saponins display potent cytotoxic activities5. In this work, we have explored several glycosyl donors for the stereoselective synthesis of steroidal glycosides through the β-O-glycosidic bond. Trichloroacetimidates6 provided the best results with sterols and was the selected methodology for further synthetic work. We have synthesised several polyhydroxylated derivatives of cholesterol and their glycosylated counterparts with the aim to overcome lipophilicity and to target cancer cells, since tumour cells have increased needs for glucose7 when compared to normal cells. All the compounds were evaluated for cytotoxicity in cancer and normal cell lines and IC50 values will be presented. The compounds synthesized exhibit antiproliferative activity in low micromolar range and in general, glycosylated sterols showed better results than the corresponding aglycones. 1 Davis, B. G. J. Chem. Soc., Perkin Trans. 1 1999, 3215–3237. 2 Olkkonen, V. M. Lipids Insights 2008, 2, 1-9. 3 Ikeda, T.; et al Biol. Pharm. Bull. 2000, 23, 364–365. 4 Francis, G.; et al British Journal of Nutrition 2002, 88, 587-605. 5 Kuroda M.; et al J. Nat. Prod. 2001, 64, 1, 88-91. 6 Deng, S.; Yu, B.; Xie, J.; and Hui, Y. J. Org. Chem. 1999, 64, 7265-7266. 7 Reuben, S. S. Current Opinion in Cell Biology 2006, 18: 598–608.
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P17
PHENOLS GLYCOSYLATION PROMOTED BY ZEOLITE HY
Ana R. Jesus,a,* Miguel M. Santos,a Ana P. Carvalho,a Amélia P. Rauter,a Fernando Ramôa Ribeiro,b Michel Guisnetb
(a) Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências
da Universidade de Lisboa, Edifício C8, 5o Piso, Campo Grande, 1749-016 Lisboa, Portugal (b) Centro de Engenharia Biológica e Química, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001
Lisboa, Portugal *[email protected]
Acid zeolites have been recently used for a variety of transformations with the advantage of being solid catalytic eco-friendly materials, known for their activity, selectivity and reusability.1 Due to their unique intrinsic architecture, zeolites are shape-selective in reactant, transition state and product, leading to reaction regioselectivity uncommon in classical procedures.
Following our group’s interest in the development of a more sustainable chemistry, we present in this communication our latest results on the glycosylation of phenolic compounds promoted by the zeolite HY (Si/Al = 2.6). Evaluation of the modifications in the crystalline structure and porosity of the catalyst with the reaction will also be considered.
In the course of our investigation using classical peracetylated sugars bearing a trichoroacetimidate leaving group2 and an array of diversely substituted phenolic compounds (Fig. 1), we realized that better yields were obtained with shorter reaction times, in strictly anhydrous conditions and using an excess of melted phenolic compound instead of solvent. A higher selectivity for the O-β-D-glycoside was noticed, with the corresponding α-anomer also being isolated in fair yields, despite the effect of the neighbouring group participation at C-2. Furthermore, and for the first time using this type of catalysts, β-C-D-glucosyl derivatives were also formed in low yield.
Pyridine adsorption experiments followed by infrared spectroscopy revealed a slightly higher density of Lewis acid centers compared to Brönsted acid centers in the zeolite structure, bearing both similar strengths. The XRD patterns revealed almost no changes on the crystallinity of the zeolite structure with the reaction, despite a pronounced decrease of its microporous volume, which has been revealed by nitrogen adsorption isotherms, most likely due to reagents/reaction products depositing.
1 Guisnet M., Ramôa-Ribeiro F., Les Zéolithes Un Nanomonde au Service da la Catalyse, EDP Sciences, France, 2006.
2 Jacobsson, M.; Malmberg, J. Carbohydr. Res., 2006, 341, 1266-1281.
1 R = CH2OAc2 R = H
R1
R1 = H, OH, OAc, OMe, NO2
R2 = OH, OAc
a), b)
a) zeolyte HY, phenolb) AcOEt, reflux, 90 min
OR
AcOAcO
AcOO CCl3
HN
OR
AcOAcO
AcO O
OR
AcOAcO
AcOR2
R1
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P18
REDUCTIVE CYCLISATION OF D-GLUCOSE-BASED UNSATURATED SUBSTRATES BY INDIRECT ELECTROCHEMICAL METHODS IN “GREEN”
MEDIA
C. Durães, A.P. Esteves,* M.J. Medeiros and C. Durães
Centro de Química, Universidade do Minho, Largo do Paço, 4704-553 Braga, Portugal * [email protected]
Cyclisation of organic substrates is of great importance in the synthesis of heterocyclic compounds which are frequently found in most drugs and fine chemicals. For example, some lignans exhibit a broad range of biological activity1. A major subgroup of lignans is comprised by tri- and tetra-substituted tetrahydrofurans the synthesis of which poses interesting and often unsolved problems of stereocontrol.
Radical cyclisation continues to be a central methodology for the preparation of heterocyclic rings and organotin reagents have dominated synthetic procedures involving radical chemistry2. Problems associated with product purification, price and toxicity have stimulated interest in the development of more user- and environmentally-friendly reagents. The electrochemical nickel-catalyzed radical-type cyclisations has been shown to be a convenient alternative for the synthesis of heterocyclic compounds3.
Our research group has developed a catalytic methodology to produce substituted tetrahydrofurans by indirect electro-reduction using Ni(II) complexes as the catalysts4.
Based in our experience in the use of acetylated D-glucose as chiral auxiliary and in order to evaluate the synthetic scope and limits of the electrochemical methodology aforementioned, we have investigated the cyclisation of substrate 1 under various experimental conditions.
O OEt
Br
OR*
OO
1
R* =
OAc
OAc
OAc
OAc
O
OR*
CO2Et
CH2
2
In this communication we present the preliminary studies of the electroorganic intramolecular cyclisation of 1 carried out in ethanol or ethanol/water mixtures, giving compound 2 as the major product. The results obtained will be discussed. Acknowledgements: We are grateful to the Fundação para a Ciência e Tecnologia for financial support of this work (PPCDT/QUI/55576/2004). 1 D.A. Whiting, “Natural Products Reports”, 1985, 191; 1987, 499; 1990, 349. 2 B. Giese, B. Kopping, T. Gobel, J. Dickhaut, G. Thoma, F. Trach., Org. React. 1996, 48, 301 (and
references therein). 3 (a) S. Ozaki, E. Matsui, J. Waku, H. Ohmori, Tetrahedron Lett. 1997, 38, 2705 (and references cited
therein) 4 (b) A.P. Esteves, E.C. Ferreira, M. J. Medeiros, Tetrahedron 2007, 63, 3006 (and references cited
therein)
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P19
C-GLYCOSYLFLAVONOIDS – ARE RARE EARTH METALS CATALYSTS A RELIABLE ALTERNATIVE FOR THEIR SYNTHESIS?
Rui Galhano dos Santos, a,* Nuno Neng,a José Nogueira,a João Bordado,b Amélia Pilar Rautera
(a) Centro de Química e Bioquímica/Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Edifício C8, Campo Grande, 1749-016 Lisboa,
PORTUGAL (b) IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering,
Instituto Superior Técnico, Av.Rovisco Pais, 1049-001 Lisboa, Portugal *[email protected]
C-glycosylphenols are embodied in a variety of biologically important natural products and the C-C bond is a great importance since it is not enzymatically degraded in vivo and is stable under physiological conditions, while the glycosidic O-C bond, part of an acetal, is easily cleaved under acidic catalysis and by enzymes. The chemical synthesis of this type of compounds has become a challenge for organic chemists, who have developed various approaches aiming at a direct access to such bioactive molecules. Efforts have been made in order to develop synthetic routes which can be easily scaled up, given that the multistep approaches usually lead to low overall yields. One of the approaches is the Fries-type rearrangement, a very straightforward and useful tool for the synthesis of this kind of products. Starting from a glycosyl template, a phenol derivative and an activator (Scheme 1), this one-pot reaction proceeds through an O-glycoside quicklly formed, which undergoes an in situ O�C-rearrangement to give regioselectively an ortho-hydroxy C-glycosylaromatic derivative in good yield.
Scheme 1. C-Glycosylation of flavonoids in aqueous medium promoted by rare earth metal triflates.
In this communication, we discuss the one-step synthesis of 8-C-glycosylnaringenin employing the Fries-type rearrangement catalyzed by rare earth metal triflates in water as well as in other environmental friendly solvents.
Acknowledgements: The authors acknowledge FCT for the PhD Grant SFRH/BD/30699/2006 and for
supporting the project PTDC/QUI/67165/2006.
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P20
ANTIDIABETIC ACTIVITY AND IDENTIFICATION OF FLAVONOID GLYCOSIDES FROM GENISTA TENERA N-BUTANOL EXTRACT
Amélia P. Rauter,a Joana Ferreira,a Alice Martins,a,* Rui G. Santos,a Carlos Borges,a Margarida
Goulart,a,b Jorge Justino,b João P. Noronha,c Rui Pinto,d Hélder Mota-Filipe,d Luísa Roseiroe
(a) Centro de Química e Bioquímica/Departamento de Química e Bioquímica da Faculdade de Ciências
da Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016 Lisboa, Portugal. *[email protected] (b) Escola Superior Agrária de Santarém, Quinta do Galinheiro, Apartado 310,
2001-904 Santarém, Portugal (c) Departamento de Química/REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da
Universidade Nova de Lisboa, 2829-516 Caparica, Portugal (d) Laboratório de Farmacologia, Faculdade de Farmácia da Universidade de Lisboa, Av. das Forças
Armadas, 1649-019 Lisboa, Portugal (e) Departamento de Biotecnologia, INETI - Instituto Nacional de Engenharia, Tecnologia e Inovação,
IP, Estrada do Paço do Lumiar, 22, 1649-038 Lisboa, Portugal
Genista tenera (Leguminosae) is a plant endemic to the island of Madeira, and is known to have an ethnopharmacological application for the control of diabetes. The antihyperglycaemic activity of its n-butanol extract has been studied in normoglycaemic, glucose-induced hyperglycaemic and streptozotocin-induced diabetic Wistar rats. Daily oral administration of the extract (200 mg/kg, b.w.) significantly lowered blood glucose levels in diabetic rats, bringing them to normal values, after 15 days of treatment. No hypoglycaemic effect was found in the oral glucose tolerance test. HPLC-DAD and HPLC-DAD-ESI-MS were employed to analyse the extract, demonstrating the presence of flavonoids, mainly flavone and isoflavone glycosides. In vitro toxicity studies showed no evidence for acute cytotoxicity or genotoxicity caused by exposure of lymphocytes to the extract.
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P21
REGIOSELECTIVE TRANSFORMATION OF CARBOHYDRATES IN AQUEOUS MEDIUM USING ELECTROCHEMICAL METHODS
Pier Parpot* and A. P. Bettencourt
Departamento de Química, Universidade do Minho, Campus Gualtar, 4710-057, Braga, Portugal
One of the major recent significance in the field of carbohydrates has been the recognition that aldonic acids have potential uses in fine chemistry. They are the raw materials in the synthesis of aldonolactones and further more in the preparation of N-alkyl aldonamide surfactants. The aldonic, alpha-keto aldonic and aldaric acids also find uses because of their solubility and sequestering capacity. With the oxidation of carbohydrates to carboxylic acids, the mass and oxygen content of the molecule increase, the character alters substantially whilst some beneficial properties, such as biocompatibility and biodegradability remain. Intermediate carbonyl compounds may be also interesting. The limited use of carbohydrates as raw materials in fine chemistry is mainly related to their overfunctionalisation and their poor solubility in most of the commonly used organic solvents. The challenge is to achieve a direct and regioselective oxidation of carbohydrates, which is difficult by classical chemical methods without a preliminary protection strategy. The electrochemical methods may constitute an alternative route for overcoming these existing technological barriers. Such transformation can be carried out in aqueous medium by associating the concepts and the methods of interfacial electrochemistry with those of heterogeneous catalysis. In this context some readily available mono- and disaccharides were oxidized regioselectively into their respective mono- and dicarboxylic acids in aqueous medium. The kinetic parameters of the reactions were determined by cyclic voltammetry. Preparative electrolyses were used to convert the mono- and disaccharides into products which were identified and quantified using chromatographic and spectroscopic methods. High yields and selectivity were obtained towards monocarboxylic acids concerning the anodic oxidation on noble metals in alkaline medium. Some dicarboxylic acids were also produced with high yields using mediators such as TEMPO.
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P22
A NEW CHEMICAL APPLICATION OF LACTOSE: SYNTHESIS OF A δδδδ-EPTULOSE
Antonino Corsaro,a,* Venerando Pistarà,a Maria Assunta Chiacchio,a and Giorgio Catelanib
(a) Dipartimento di Scienze Chimiche, Università di Catania, viale A. Doria 6 I-95125 Catania, Italy, *[email protected]
(b) Dipartimento di Chimica Bioorganica e Biofarmacia, Università di Pisa, via Bonanno 33 I-56126 Pisa, Italy
Recently we have started a research program on the chemical valorization of lactose,1 the most abundant reducing disaccharide, studying its conversion in new useful intermediates for the synthesis of cyclitols and carbasugars. As extension of these studies, here we report the conversion of lactose into a δ-eptulose derivative.
Our approach starts from the 5'-exo-pyranoside 1, easily obtained with a protection/deprotec-tion/elimination sequence from lactose,2 which was cyclopropanated according to the Furukawa modified Simmons/Smith procedure, to give the spiro-adduct 23 in nearly quantitative yield. The spiro-adduct 2 was then subjected to electrophilic ring opening by treatment with mercuric trifluoroacetate in dry methanol affording, after exchange with NaCl, an anomeric mixture (1:1.5) of the two organomercuric chlorides 3. Upon reductive demercuriation, these latter afford the 6,7-dideoxy-1,5-bis-glycosides 4, masked forms of the 1,5-dicarbonyl heptose 5, which is obtained by acidic hydrolysis of 4 together with D-glucose. The δ-eptulose 5 exists as a 1:2.7 α- and β-furanose mixture in CD3CN/D2O solution.
O
(MeO)2HCO
O
OO
G =
OO
O
BnOGOO
O
BnOG
1 2
OO
O
BnOG
3
ClHg
OMe
OO
O
BnOG
4
OMe
OHO
HO
BnOO
5
To our best knowledge this is the first example about the synthesis of a 6,7-dideoxy-δ-eptulose from a spiro-lactose reported in literature and outlines a new route for the stereoselective transformation of lactose into new interesting sugars, expanding, thus, the series of applications directed toward an economical valorisation of this natural disaccharide, by-product of the cheese-industry.
1 Corsaro, A.; Catelani, G.; D’Andrea, F.; Fisichella, S.; Mariani, M.; Pistarà, V. Environ. Sci. Pollut. Res. 2003, 10, 325-328.
2 Catelani, G.; Corsaro, A.; D’Andrea, F.; Mariani, M.; Pistarà, V.; Vittorino, E. Carbohydr. Res. 2003, 338, 2349-2358.
3 Corsaro, A.; Chiacchio, M.A.; Pistarà, V.; Rescifina, A.; Vittorino E. Tetrahedron, 2008, 64, 8652-8658.
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P23
SYNTHESIS OF NEW SUGAR-BASED SURFACTANTS COMBINED CATALYSTS : TOWARDS GREENER CATALYTIC PROCESSES
Mathieu Delample, Ayman Karam, Nicolas Villandier, Joël Barrault and François Jérôme*
Laboratoire de Catalyse en Chimie Organique, Université de Poitiers/CNRS
40 Avenue du recteur Pineau, 86022 Poitiers, France, *[email protected]
Recently, we found that use of glycerol as green solvent for catalysis has similar properties than water. Indeed, glycerol is natural, highly hydrophilic, non toxic, abundant, biodegradable and very cheap. Moreover, glycerol has a higher boiling point and a lower vapour pressure.
However, design of efficient catalytic processes in glycerol requires chemists to overcome (i) the low solubility of most of organic substrates and (ii) the intrinsic reactivity of glycerol. In order to circumvent these issues, we synthesized a new family of sugar based “surfactant-combined-catalysts” (SCCs). These SCC, named aminopolysaccharide (AP) (Scheme 1) are highly interesting owing firstly to their amphiphilic properties and secondly because the hydrophobic core is surrounded by some amino moieties which can act as basic catalysts.
OOR1
O
OR1
OOR1
OR1
O O OO
OR1
OHOH
OR1
OR1
OHO O O O
O
OHOH
OR1
O
OR1
O
OHOH
OR1
OR1
O O OO
OR1
OHOH
OR1
OR1
OH
NaIO4
H2O/24hn n
Dodécylamine
MeOH/H2O (80/20 vol)
Pd/C, H2 (10 bars)
25°C, 15h
OOR1
O
OR1
OOR1
OR1
O O OO
OR1
OHOH
OR1
OR1
OHNH NH NH NH
R2R2
R2 R2
n
R1 = -(CH2CH2O)nH R2 = -(CH2)7CH3, DSNH=0.5
Scheme 1 : Synthesis of amphiphilic AP catalysts.
On the basis of these features, we found that APs were more efficient than commonly used basic catalysts for performing various selective base-catalyzed reactions in glycerol (ring opening of epoxides, Knoevenagel reactions, etc…). Close control of the reaction selectivity was achieved owing to the formation of catalytic hydrophobic pockets. As a second alternative, we recently found that APs were also able to stabilise some palladium nanoparticles (6 nm).We are able to perform highly selective Heck coupling. Indeed, owing to their amphiphilic properties, we will show that Pd/AP catalysts were more active than known palladium catalysts.
Syntheses of APs and their ability to form emulsions in glycerol is presented. Influence of the amount of fatty chain and the amphiphilicity of APs on the catalytic results is also discussed.
A.Karam, N.Villandier, M.Delample, C.Klein Koerkamp, J-P Douliez, R.Granet, P.Krausz, J.Barrault, F.Jérôme, Chem.Eur.J, 2008, 14, 33, 10196-10200. Y.Gu, F.Jérôme, J.Barrault, Adv.Synth.Cat, 2008, 350,13, 2007-2012. Unpublished results for Heck coupling with Pd/AP.
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P24
SURFACE-ACTIVE AGENTS FROM RENEWABLE RESOURCES
Tiago Fonseca, Inês Raposeiro, João Bordado*
IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering,
Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal *[email protected]
Saccharides/Sugar Fatty Acid Esters (SFAE) are widely used in food, cosmetic and pharmaceutical industries due their surface active properties. Large production of SFAE for these applications requires high quality and purity, which increase the final product cost. For specific applications, such as detergents and asphalt emulsificants, this requirement it is not necessary, allowing the use of different raw materials, particularly from renewable resources. In fact, the majority of surface-active products in the surfactant market are still derived from petroleum. The expected growth rate of this sector has been a driven force for the development of new cheap, environmentally-friend product with minimal health risk1.
In the present work, the synthesis of SFAE was carried out by transesterification of sucrose and fatty acid methyl esters (FAME) from Colza oil. Initially several studies, using this heterogeneous system, were performed with different catalysts at low temperature. However, as the surface contact area between solid sucrose and liquid FAME conditions the reaction kinetics, an alternative solution had to be considered. An organic solvent, DMSO, which dissolves both substrates, was introduced in the reaction to obtain a monophasis system and to facilitate the contact. Nevertheless, the presence of suspended particles (sucrose) in the reactor indicated low conversion rate. A different synthesis method had to be explored in order to dissolve enough substrate to carry out the reaction. Therefore, in a first step, sucrose was acetylated with acetic anhydride. The reaction was performed on a 1L batch reactor, during 2 days, at 70ºC, under N2 atmosphere to assure oxygen exclusion. The catalyst used was sodium acetate. On a second step, FAME was introduced in the glass vessel for the transesterification of polyacetylated sucrose. This reaction was carried out at the same temperature but under vacuum. Several low-temperature catalysts were tested comparatively. Process was turned to avoid formation of oligomeric saccharides and to control viscosity of the final surfactant raw material. The HLB of final products displays different surfactant properties according with the stoichiometry of the reaction. Further studies will be made in order to characterize the sugar esters products such as emulsion stability and surface tension in collaboration with other industrial partners. Preliminary results seem to indicate a promising process to produce SFAE from two substrates abundant, cheap and derived from renewable resources.
Acknowledgments: The authors acknowledge the projects: EU Integrated Project, Contract nº 026515-2, and POCTI/BIO/55789/2004, as well as the interest and collaboration of the industrial partners of the Bioproduction project. 1 Yoo, I.S., Park, S.J., Yoon, H.H. J. Ind. Eng. Chem. 2007, 13, 1-6.
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P25
CARBOHYDRATES AS CHIRAL INDUCERS IN ASYMMETRIC CATALYSIS : COPPER(II) COMPLEXES OF SUGARS ESTERS & AMIDES DERIVED FROM
2,2'-BIPYRIDINE FOR ENANTIOSELECTIVE ELECTROPHILIC FLUORINATION
Aurélie Assalit,a,b,* Thierry Billard,a Bernard Langlois,a Yves Queneau,b Stéphane Chambert,b Diane Coe,c
(a) Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, Laboratoire SERCOF, 43
Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France, *[email protected] (b) Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie
Organique, INSA-Lyon, Bât. Jules Verne, 20 Avenue Albert Einstein, Villeurbanne F-69621, France (c) Medicines Research Centre, RespiratoryCEDD, GlaxoSmithKline, Gunnels Wood Road, Stevenage
SG1 2NY, United Kingdom Due to their unique properties, fluorinated compounds have been found to be potent templates in both the agrochemical and pharmaceutical industry. It is therefore not surprising that the interest in developing new synthetic routes for the introduction of fluorine is increasing. A large variety of strategies have been employed in the last few years for enantioselective fluorination using N-fluorosultams1 or N-fluoro ammonium salts derived from Cinchona alkaloids1, transition metal complexes2 and more recently organocatalysts2
. However, the natural chiral pool is far from being fully explored; in particular, carbohydrates tend to be remarkable chiral auxiliaries and ligands3 offering readily available, varied and naturally enriched templates. Bipyridinic systems have been widely used as Cu(II) ligands. Therefore various 2,2’-bipyridines substituted by carbohydrate amide or ester moieties were synthesised and considered as Cu(OTf)2 ligands. The resultant complexes have been utilised with N-fluorobenzenesulfonimide as achiral fluorinating agent to achieve encouraging results in the asymmetric fluorination of cyclic and acyclic β-ketoesters. 1 Ibrahim H., Togni A. Chem. Comm. 2004, 1147. 2 Pihko P.M. Angew. Chem. Int. Ed. 2006, 45, 544. Bobbio C., Gouverneur V. Org. Biomol. Chem. 2006, 4, 2065. 3 Boysen M.M.K. Chem. Eur. J. 2007, 13, 8648. Diéguez M., Claver C., Pámies O. Eur. J. Org. Chem. 2007, 4621.
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P26
NOVEL SUPRAMOLECULAR DIMERS OF CYCLODEXTRIN DERIVATIVES
F. Hamon,a B. Violeau,a F. Turpin,b E.M. Belgsir,b Y. Cenatiempo,b F. Djedaïni-Pilard, c C. Lena,*
(a) Synthèse et Réactivité des Substances Naturelles, UMR6514 Université de Poitiers-CNRS
40 avenue du Recteur Pineau, 86022 Poitiers, France (b) BIOCYDEX, 40 avenue du Recteur Pineau, 86022 Poitiers, France
(c) Laboratoire des Glucides, UMR6219 Université de Picardie Jules Verne-CNRS 33 rue Saint Leu, 80039 Amiens, France
Cyclodextrins are a family of cyclic oligomers composed of α-(1 → 4)-linked D-glucopyranose units in 4C1 chair conformation. As a consequence of this peculiar structure, cyclodextrins feature a conical cavity that is essentially hydrophobic in nature and can include several types of guest molecules of appropriate size to form inclusion complexes. During the last three decades, syntheses, properties and applications of monomeric and dimeric cyclodextrin derivatives have been the subject of many works.1-3 It is noteworthy that covalent dimers of cyclodextrins present association’s constants generally superior to that of the monomer constituting them.
In the present work, syntheses and properties of novel supramolecular dimers of cyclodextrin derivatives having aden-9-yl and thym-1-yl moieties are discussed. 1 Villalonga, R.; Cao, R.; Fragoso, A. Chem. Rev. 2007, 107, 3088–3116. 2 Wenz, G.; Han, B.H.; Muller, A. Chem. Rev. 2006, 106, 782-817. 3 Hapiot, F.; Tilloy, S.; Monflier, E. Chem. Rev. 2006, 106,767-781.
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P27
CHEMICAL MODIFICATION OF A BACTERIAL POLYSACCHARIDE FOLLOWING HOMOGENEOUS OR HETEROGENEOUS PROCEDURES
Rudy Covisa, Catherine Ladavièreb, Emmanuelle Mariea, Alain Duranda,c*
(a) Laboratoire de Chimie Physique Macromoléculaire, UMR 7568 CNRS - Nancy-University,
ENSIC, 1 rue Grandville, BP 20451, F-54001 Nancy cedex, France, [email protected] (b) Laboratoire des Matériaux Polymères et des Biomatériaux, UMR CNRS 5223,
Bâtiment ISTIL, 15 Boulevard Latarjet, 69622 Villeurbanne cedex, France (c) Current address : Laboratoire des Sciences du Génie Chimique, UMR 6811 CNRS,
ENSIC, 1 rue Grandville, BP 20451, F-54001 Nancy cedex, France
This work deals with the preparation of amphiphilic polymers by chemical modification of dextran, a neutral bacterial polysaccharide consisting chiefly of α-1,6 linked glucose units1. This highly hydrophilic polymer was used a raw material for the preparation of neutral polymeric surfactants2. In that work, various amounts of hydrocarbon chains (-C10H21) were attached onto dextran repeat units by reacting the polysaccharide with epoxydodecane in the presence of hydroxide ions thus forming ether links between the backbone and the hydrocarbon tails. Two reaction procedures were compared, one carried out in dimethylsulfoxide (DMSO) a polar solvent in which both dextran and epoxydodecane can be dissolved and the other in an aqueous medium in which epoxydodecane is dispersed thanks to the use of a surfactant. Whatever the followed procedure, the reaction between dextan and epoxydodecane is competing with the anionic polymerization of epoxydodecane. The latter reaction was evidenced in both procedures (using various techniques like size exclusion chromatography and MALDI-TOF mass spectrometry) and mainly results from the use of hydroxide ions. Their replacement by a less nucleophilic base almost suppressed the side reaction but without increasing the yield of the reaction with dextran. The effects of various reaction parameters on the structural characteristics of the modified dextran were investigated with both reaction procedures (in DMSO and in water). The two reaction procedures are also compared with regard to the obtained extents of dextran modification. The amphiphilic polymers prepared can be used in the preparation of nanoparticles used in drug delivery applications according to their structural characteristics3.
1 Nordmeier, E. J. Phys. Chem. 1993, 97, 5770. 2 Rouzes, C., Durand, A., Leonard, M., Dellacherie, E. J. Colloid Interface Sci. 2002, 253, 217. 3 Rotureau, E., Marie, E., Leonard, M., Dellacherie, E., Camesano, T. A., Durand, A. Colloids and Surfaces A 2006, 288, 62.
112
O
OHOH
OHOH
O O CH3
3O
OHOH
OH
OHO O CH3
3O
OOH
OHOH
OH
CH3
2
tetradecyl
glucuronate
dodecyl
galacturona
te
hexyl
glucoside
P28
CHEMICAL AND ENZYMATICAL MODIFICATIONS OF SUGAR DERIVED FROM LIGNOCELLULOSE
Gaëtan Richard,a,b Pascal Laurent,a,b Katherine Nott,b Aurore Richel,a,b Murielle Helleputte,b Jean-Paul
Wathelet,b Michel Paquota,*
(a) Unit of Biological Chemistry, Gembloux Agricultural University, Passage des Déportés, 2, B – 5030 Gembloux, Belgium * [email protected]
(b) Unit of General and Organic Chemistry, Gembloux Agricultural University, Passage des Déportés, 2, B – 5030 Gembloux, Belgium.
Actually, biorefinery is increasingly considered as a promising alternative to petroleum chemistry, since it aims at not only the replacement of fossil energy but also the development of chemicals from biomass, with applications such as detergents, phytopharmaceuticals, solvents, plastics, etc.
The valorisation of carbohydrates from renewable raw materials1 is currently the subject of numerous researches2. In this context, the synthesis of new surfactants derived from the sugars issued from the hydrolysis of lignocellulose was undertaken by chemical or enzymatic routes. In this poster, the examples of glucose, cellobiose and uronic acids3 will be discussed.
Whatever the way used, the reaction conditions (use of a catalyst, protection/deprotection steps, type of solvent, presence of co-solvent, reactant concentrations, etc) were optimized to yield a panel of carbohydrate derivatives (some examples of the structures obtained are given above). These differ by the nature of the alkyl chain (in length and in degree of saturation), the type of chemical bond (amide, ester, thioester, acetal), and the position of substitution.
The impact of these differences on the techno-functional properties of the modified sugars will be evaluated.
1 Lichtenthaler, F.W. Carbohydrates as Renewable Raw Materials: a Major Challenge of Green Chemistry IN: Methods and Reagents for Green Chemistry: an introduction; Tundo, P., Perosa, A., Zecchini, F. Eds.; Wiley-Interscience, John Wiley & Sons, Inc., Hoboken, New Jersey, 2007, 23-63.
2 Queneau, Y., Chambert, S., Besset, C., Cheaib, R., Carbohydr. Res., 2008, 343 (12), 1999–2009. 3 Blecker, C., Danthine, S., Pétré, M., Lognay, G., Moreau, B., Vander Elst, L., Paquot, M., Deroanne,
C., J. Coll. Interf. Sci., 2008, 321 (1), 154–158.
113
P29
OXIDATION OF POLYSACCHARIDES: FROM STOICHIOMETRIC PROCESSES TOWARD CATALYTIC CLEAN ROUTES
Svetlana L. Kachkarova, Pierre Gallezot and Alexander B. Sorokin*
Institut de Recherches sur la Catalyse et l’Environnement de Lyon, IRCELYON, UMR 5256, CNRS –
University Lyon 1, 2 av. A. Einstein, 69626 Villeurbanne, France [email protected]
Oxidative transformation of polysaccharides provides industrially viable products for different applications aiming to replace materials derived from fossil feedstock. Traditional approaches are based on the stoichiometric oxidants, like NaOCl, NaIO4, etc, which constitutes environmental problems. The quest for an efficient and clean oxidation methods still remains an important challenge.1 Here we report on the comparative analysis of methods for selective oxidation of polysaccharides, including stoichiometric and catalytic approaches.
Then, a novel green catalytic procedure for the oxidation of polysaccharides developed in our laboratory using iron tetrasulfophthalocyanine (FePcS) as a cheap and readily accessible catalyst and H2O2 as green oxidant in water will be discussed.2,3
In the presence of trace amount of catalyst turnovers of more than 2000 have been attained. The efficiency of utilisation of H2O2 to form carbonyl and carboxyl groups reached 80 %. The products were characterised by carbonyl and carboxyl substitution degrees, residual Fe content and by 13C NMR, TGA, SEM methods. Importantly, no acids, bases, buffers or organic solvents are used. Only small amounts of water, H2O2 and a cheap bio-inspired catalyst are used for clean one step modification of polysaccharides without any production of waste/side products.
The scope of this method has been extended to the oxidation of different polysaccharides:
Due to flexibility of this method hydrophilic tailor made materials can be quantitatively obtained just by changing of the reaction conditions to provide the products with desired content of carboxyl and carbonyl groups according to application profile.
1 Bragd, P., Besemer, A.C., van Bekkum, H. Carbohydr. Polym. 2002, 49, 397 and references therein. 2 Sorokin, A.B., Kachkarova-Sorokina, S.L., Donzé, S., Pinel, C., Gallezot, P., Top. Catal., 2004, 27,
67-76. 3 Kachkarova-Sorokina, S.L., Gallezot, P., Sorokin, A.B., Chem Commun., 2004, 2844-2845.
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OH
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OH
O
O
OH OH
OH
O
O
OH OH
OH
O
0.00004 mol % catalyst
H2O2
90-99 % yield no wastes
OO
OHOH
CH2OH
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OH
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OHOH
CH2OH
OCH
2OH
α−α−α−α−cellulose and its hydroxyethyl- and carboxymethyl derivatives
OHO
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OH
OH
O
O
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OHOH
O*
* x y
Guar gum
O
O
OHO
OHOH
OH
OOH
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OH
O
OH
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n = 2 - 60
Inulin
114
P30
ANALYSIS OF DFAS IN PREBIOTIC CARAMELS: A COMBINATION OF HPAEC-PAD, MS AND STEREOSELECTIVE SYNTHESIS
Elena Suárez-Pereira,a Carmen Ortiz Mellet,a* Antoine Fournez,b David Lesur,b Serge Pilard,b and
José M. García Fernandezc*
(a) Dpto. de Química Orgánica, Facultad de Química, Univ. Sevilla, Sevilla E-41012, Spain, *[email protected]
(b) Lab. des Glucides UMR6219 and Analytical Platform, Université de Picardie Jules Verne, F-80039 Amiens, France
(c) Instituto de Investigaciones Químicas, CSIC - Univ. Sevilla, E-41092 Sevilla, Spain, *[email protected].
The discovery of difructose dianhydrides (DFAs) as the main components of the oligosaccharide fraction of caramels1 has brought forward the need of developing efficient analytical procedures that could be applied to food and biological samples for the identification and quantification of the different diasteroisomers. Defaye and coworkers have applied successfully gas chromatography (GC) to the analysis of DFAs in commercial caramels.2 Derivatization of the sample by a sequence of reactions that involves oximation and trimethylsilylation is, however, required. The above protocol allows the separation of the 13 DFA diastereoisomers identified in fructose caramels. An additional mixed fructose-glucose dianhydride has been identified in sucrose caramel, although the retention time for this minor component overlaps with the peak of sucrose. While GC analysis of DFAs represents a quite significant advance, the necessity to subject the sample to prior derivatization represents a drawback. An additional problem is the lack of pure DFA standards for calibration of the method and determination of the corresponding response factors. This is especially delicate in view of the difficulties to separate pure DFAs from mixtures. In an attempt to overcome these limitations, we have examined the suitability of High Performance Anion-Exchange Chromatography coupled with Pulse Amperometric Detection (HPAEC-PAD) for the separation and analysis of DFAs and its application to DFA enriched caramels (prebiotic caramels)3 obtained by acid resin-catalyzed caramelization of D-fructose, in combination with MS analysis. HPAEC-PAD is particularly well suited for the analysis of unprotected carbohydrate derivatives without the need of any prior derivatization. We have observed that this technique allows separation of DFAs according to their core structure, pyranose derivatives showing lower retention times as compared with furanose derivatives. In parallel, we have investigated new approaches for the stereoselective synthesis of individual DFA diastereomers that could be used to unequivocally identify the peaks in the chromatogram and as calibration standards. For this purpose, we have exploited our recently reported approach using xylylene groups as cyclic protecting groups for 1,2-diol segments or as linear tethers between the reacting fructose subunits.4
1 Defaye, J.; García Fernández, J. M. Carbohydr. Res. 1994, 256, C1-C4. 2 Ratsimba, V.; García Fernández, J. M.; Defaye, J.; Nigay, H.; Voilley, A. J. Chromatogr. A 1999, 844,
283-293. 3 Rubio Castillo, E. M.; Gómez-García, M.; Ortiz Mellet, C.; García Fernández, J. M.; Zarzuelo Zurita,
A.; Gálvez Peralta, J. J.; Duval, R. “New caramels with high content in prebiotic oligosaccharides, their preparation and use”. ES/P200700675, 2007; PCT/ES2008/000129, 2008.
4 Garcia-Moreno, M. I.; Benito, J. M.; Ortiz Mellet, C.; García Fernández, J. M. Molecules 2008, 13, 1640-1670.
115
P31
SYNTHESIS OF ALKYLATED AND THIOALKYLATED MALTODEXTRINE DERIVATIVES AND EVALUATION OF THEIR ANTIMICROBIAL AND ANTI-
INFLAMMATORY PROPERTIES
Vincent Moreau,a* Nicolas Thiebault,a David Lesur,a Paul Godé,a Patrice André,b Jean-Christophe Archambault,b F. Djedaïni-Pilarda
(a) Laboratoire des Glucides, CNRS-UMR 6219, Institut de Chimie de Picardie, Université de Picardie
Jules Verne, 33 rue St Leu, 80039 Amiens, France, *[email protected] (b) LVMH, Laboratoire de R&D Branche Parfums et Cosmétiques, 45 800 St Jean de Braye, France
Since the first patent describing their use in detergents in 1934, alkylated carbohydrates have found applications in multiple areas. Amongst these can be cited their use as model biomembranes1 or their potential antitumor activities.2 They can also form liquid cristals3 and have found practical uses as surfactants and non-ionic detergents.4 It was generally recognized that n-alkyl glycosides containing a C8 and C12 alkyl chain showed a broad spectrum of antimicrobial activity. Among them, those with n-dodecyl groups were particularly effective against Gram-positive strains as well as fungal strains.5
With the aim to study their antimicrobial and anti-inflammatory properties, the synthesis of a series of alkylated and thioalkylated maltodextrines of various DP has been undertaken. 6-deoxy-6-alkylthiomaltotriose derivatives6 as well as S-alkyl- and O-alkyl- derivatives of maltose, maltotriose and maltoheptaose have been obtained and their antimicrobial and anti-inflammatory activities evaluated. While thioalkylated compounds displayed weak or no activity, O-alkylmaltodextrine derivatives showed a great antimicrobial and anti-inflammatory potential, alone or in mixtures for which an interesting synergic effect has been observed.7
Syntheses and biological evaluations will be presented.
1 Ahlers, M., Müller, W., Reichert, A., Ringsdorf, X.; Venzmer, J. Angew. Chem. Int. Ed. Engl. 1990, 29, 1269-1285.
2 Gorbach, V. I.; Krosikova, I. N.; Luk’yanov, P. A.; Loenko, Y. N.; Solov’eva, T. F.; Ovodov, Y. S.; Deev, V. V.; Pimenov, A. A. Carbohydr. Res. 1994, 260, 73-82.
3 Jeffrey, G. A.; Wingert, L. M. Liq. Cryst. 1992, 12, 179-202. 4 Koll, P.; Oelting, M. Tetrahedron Lett. 1986, 27, 2837-2838. 5 Matsumura, S.; Imai, K.; Yoshikawa, S.; Kawada, K.; Uchibori, T. J. Am. Oil. Chem. Soc. 1990, 67,
996-1001. 6 Thiebault, N., Lesur, D., Godé, P., Moreau, V., Djedaïni-Pilard., F. Carbohydr. Res., 2008, 343, 2719-
2728. 7 André, P., Archambault, JC., Thiebault, N., Moreau, V., Djedaïni-Pilard,F. « Utilisation d’au moins un
glycoside d’alkyle en tant qu’agent anti-vieillisement et/ou calmant des peaux sensibles dans des compositions cosmétiques, et méthodes de soins cosmétiques utilisant lesdites compositions » déposé le 02 avril 2008, N° 1000027678, N° demande 0852193
116
P32
DERMO-COSMETIC PERFORMANCES OF NEW FORMULATIONS CONTAINING HALURONATE BUTYRIC AND FORMIC ESTERS
M. Bosco,a,* L. Cocchi,b M. Fabbian,a R. Gianni,a F. Picotti,a L. Stucchi,a A. Trevisana
(a) Sigea S.r.l.,Area Science Park, Padriciano 99, 34012 Trieste, Italy, *[email protected]
(b) SIGMAR Italia s.p.a., via Sombreno, 11 – 24011 Almè, Bergamo, Italy Hyaluronan (HA) is a glycosaminoglycan which is involved in many physiological functions such as joint lubrication, cell motility, cell adhesion and differentiation. HA is present in the extra-cellular matrix of skin where it plays a fundamental role in hydrating, balancing the electrolyte equilibrium and stimulating tissue repair processes.
Its use in dermo-cosmetic applications is continuously growing both as a component of topic creams and as injectable gel or viscous solution (dermal filler) in the attempt to compensate the loss of endogenous HA.
Sigmar Italia developed two formulations (P07044 and P07045) containing one butyric and formic ester of HA (HAbut) that was obtained and patented by Sigea (MI20072237). This new-generation derivative of HA offers an optimal modulation of the hydrophilic-lipophilic balance and an higher resistance to enzymatic degradation with respect to native HA.
All the components of the formulations have been chosen in order to enhance the performances of the active molecule HAbut and provide the optimum sensorial profile.
The performances of these creams have been tested on healthy volunteers and compared to the corresponding formulations without HAbut. After one month of application on the skin, a lasting increase hydration and elasticity (R2 parameter) was exhibited by all the volunteers; the average improvement of the skin parameters was highly significant (p<0.0001).
oH3C
O
O
O-Na+
O
O
OH
OO
O
NH
HO
O n
CH3
O
117
P33
NEW HYALURONIC ACID DERIVATIVES AND THEIR APPLICATIONS
M. Bosco,a M. Fabbian,a R. Gianni,a F. Picotti,a,* L. Stucchi,a A. Trevisana
(a) Sigea S.r.l., Area Science Park, Padriciano 99, 34012 Trieste, Italy, *[email protected]
Hyaluronan (HA) is a glycosaminoglycan composed of a repeating unit of D-glucuronic acid and D-N-acetylglucosamine. This polysaccharide has an extended conformation and produce high viscous solutions.
HA is the main constituent of extra-cellular matrix and plays a fundamental role in many physiological functions such as joint lubrication, tissue hydration, cell motility, cell adhesion and differentiation in all vertebrates.
The turnover of HA metabolism is fast: its half life varies from 2-3 weeks in cartilage to few minutes in blood stream.
Sigea developed and patented new classes of soluble and cross-linked HA derivatives which are obtained in simple way under mild reaction conditions and by using safe reagents.
Mixed esters of butyric and formic acids on hyaluronan are described. They exhibit enhanced biostability, improved rheological properties and can be sterilized by steam. The modulation of their final physico-chemical properties can be obtained by changing the reaction conditions.
Enzymatic degradation studies, by means of bovine testicular Hyaluronidase and Esterases, of soluble HA-butyrate derivatives and of HA-butyrate hydrogels are described. The degradation kinetics were investigated using different concentration ratios of enzyme and substrate.
The linear HA butyric esters are degraded following different kinetic behaviours depending on the esterification degree.
The degradation process of the crosslinked derivatives was followed by measuring rheological properties (G’ and G”) in comparison with HA crosslinked medical devices available on the market.
118
P34
REACTIVITY OF SUCROSE-LIKE TRISACCHARIDES: RAFFINOSE AND MELEZITOSE
Céline Besset,a,b Stéphane Chambert,a,b Alain Doutheau,a,b Bernard Fenet,c Jérôme Guilbot,d Hervé
Rolland,d Sébastien Kerverdo,d Yves Queneaua,b
(a) INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne. [email protected]
(b) CNRS, UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université Lyon 1 ; INSA Lyon ; CPE Lyon.
(c) Centre commun de RMN, Université Lyon 1, Bat Curien, 69622 Villeurbanne (d) SEPPIC, 127 chemin de la Poudrerie, BP 228, 81105 Castres cedex
After our studies on the reactivity of sucrose,1 we extended our investigations to two trisaccharides possessing a sucrose basis : melezitose (3’-O-α-glucopyranosyl sucrose) and raffinose (6-O-α-galactopyranosyl sucrose). One aspect of their chemistry lies on the relative reactivity of their primary alcohol functions, which has been studied by comparing their behavior under Mitsunobu conditions. This reaction is usually very selective towards less hindered positions in sugars, though the presence of many hydroxyl groups often results in a competition between intermolecular esterification and intramolecular etherification.2
The results on the esterification of these sugars by palmitic acid are presented as well as the detailed studies of the 1D and 2D NMR experiments which allowed the structural identification of the major compounds, namely melezitose diester 1 and anhydro raffinose 2.3 Such compounds can serve as reference compounds in the search of new processes towards carbohydrate-based surfactants having larger polar moieties compared to many existing ones.4
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HO OHO
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OH
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61'
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6"
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1"
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melezitose raffinose
1 Queneau, Y., Jarosz, S., Lewandowski, B., Fitremann, J. Adv. Carbohydr. Chem. Biochem. 2007, 61,
217-292, 2 Molinier, V., Fitremann, J., Bouchu, A., Queneau Y.,Tetrahedron Asymmetry 2004, 15, 1753-1762. 3 Besset, C., Chambert, S., Queneau, Y., Kerverdo, S., Rolland, H., Guilbot, J. Carbohydr. Res. 2008,
343, 929-935. 4 Queneau, Y. Chambert, S., Besset, C., Cheaib. R. Carbohydr.Res. 2008, 343, 1999-2009.
119
P35
THE USE OF ISOSORBIDE DERIVATIVES AS BIO-SOURCED ALTERNATIVES TO PETROLEUM-DERIVED PRODUCTS FOR DETERGENT APPLICATIONS
Morgan Durand, Ying Zhu, Valérie Molinier* and Jean-Marie Aubry
LCOM - UMR CNRS 8009 - Oxydation et Physico-Chimie de la Formulation,
Ecole Nationale Supérieure de Chimie de Lille, 59652 Villeneuve d'Ascq, France, *[email protected]
Isosorbide is a diol readily obtained from starch that can be used as a polar building block for the synthesis of derivatives ranging from solvents to surfactants. Dimethylisosorbide ether (DMI) is already recognized as an environmentally friendly solvent. It is currently used in cosmetics and pharmacy but its unique properties make this solvent a good candidate for many other applications1. Monoalkyl derivatives of isosorbide are non-ionic hydrotropes that could be potential substitutes to short-chain glycol ethers2. Other diether isosorbide derivatives such as diethylisosorbide (DEI) or dipropylisosorbide (DPI) ethers have never been characterized so far, and may have similar interesting physicochemical properties. Firstly, some significant physicochemical properties of DMI, DEI, and DPI, such as water solubility and octanol water partition coefficient, have been investigated. The use of these isosorbide derivatives as bio-sourced alternatives to petroleum-derived products for applications such as compatibilizers in liquid detergent formulations has been evaluated and compared to typical coupling agents.
Fig. 1 Representation of the extent of the liquid crystal regions in the partial ternary diagram Synperonic A7/Water/Hydrotrope at 25°C. Lα = Lamellar phase, H1 = Hexagonal phase
The influence of DMI and some reference hydrotropes / cosolvents on the phase diagram of a non-ionic surfactant, namely SYNPERONIC A7 (C13/C15 alcohol with 7 ethylene oxide group) has been investigated using polarising microscopy and rheological measurements (figure 1). The influence of hydrotropes on the cloud point temperature and on the destabilization of liquid crystal regions has been evaluated. Dimethylisosorbide (DMI) reveals to have interesting coupling properties for the former applications.
1 This studies have been partially supported by Roquette Frères, the world wide leading company for polyols like sorbitol and isosorbide. The use of DMI as a solvent is notably covered by the international patent applications WO 2006120342 and WO 2006120343 filed by Roquette Frères.
2 Zhu, Y., Durand, M., Molinier, V., Aubry, J.-M. Green Chem. 2008, 10, 532-540.
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P36
MULTI-LACTOSIDES BASED ON CARBOHYDRATE SCAFFOLDS FOR STUDYING SUGAR-LECTIN INTERATIONS
S.G. Gouin,a,* J. Kovenskya
(a) Laboratoire des Glucides, UMR 6219, Université de Picardie Jules Verne, 33 rue Saint Leu,
80039 Amiens, France. [email protected]
Carbohydrate-lectins interactions play a pivotal role in many biological events including inflammation, immune response, apoptosis, tumour metastasis or viral and bacterial infections.1 The generally low affinity of monovalent ligands for their putative lectins can be overcome by using polyfunctional scaffolds displaying structurally well defined saccharides units. Hundreds of synthetic multivalent glycomimetics with diverse spatial arrangement, number of epitopes, and degree of freedom have been synthesized. Carbohydrates have not been much investigated as scaffolds compared to dendrimers or polymers. For in vivo applications, multivalent ligands based on carbohydrate scaffolds keeping some free hydroxyl groups may be more appropriate. Improved hydrophilicity and pharmacokinetics may be expected, for instance, as compared with peptidic, aromatic or polymeric scaffolds.
The goal of our research activities is to develop a new class of multivalent ligands based on a carbohydrate scaffold. We first used an efficient methodology for the regioselective azidation of unprotected saccharides. We have then evaluated the possibility of grafting ligands onto the scaffolds by click chemistry.2 A series of multi-mannosides and multi-lactosides with different valencies and spatial orientations have been synthesized. Synthetic methodologies, dynamic molecular studies and binding affinities of the glycoconjugates for lectins will be presented.
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1 For reviews on lectins: (a) Lis, H.; Sharon, N. Chem. Rev. 1998, 98, 637-674.(b) Gabius, H.-J. Adv.
Drug Deliv. Rev. 2004, 56, 421-424. (c) Ambrosi, M.; Cameron, N.R.; Davis, B.G. Org. Biomol. Chem., 2005, 3, 1593-1608.
2 Gouin, S.G.; Kovensky, J. Tetrahedron Lett. 2007, 281, 2875-2879. Gouin, S.G. ; Bultel, L.; Falentin, C.; Kovensky, J. Eur. J. Org. Chem, 2007, 7, 1160. Gouin, S.G.; Vanquelef, E.; García Fernández, J.M.; Ortiz Mellet, C.; Dupradeau, F-Y.; Kovensky, J. J. Org. Chem. 2007, 72, 9032-9045.
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P37
GENE DELIVERY VEHICLES BASED ON AMPHIPHILIC ββββ-CYCLODEXTRIN “CLICK CLUSTERS”
Alejandro Méndez-Ardoy,a Marta Gómez-García,b Carmen Ortiz Mellet,a* M. Dolores Girón-González,c Natalia Sevillano-Tripero,c Rafael Salto-González,c* Francisco Santoyo-González,d
and José M. García Fernándezb*
(a) Dpto. de Química Orgánica, Facultad de Química, Univ. Sevilla, Sevilla E-41012, Spain, *[email protected]
(b) Instituto de Investigaciones Químicas, CSIC - Univ. Sevilla, E-41092 Sevilla, Spain, *[email protected]
(c) Dpto. de Bioquímica y Biología Molecular II, Facultad de Farmacia, Univ. de Granada, E-18071 Granada, Spain, *[email protected]
(d) Dpto. de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología, Univ. de Granada, E-18071 Granada, Spain.
We have recently reported a modular synthetic strategy for the preparation of polycationic
amphiphilic cyclodextrins (CDs) that allows the installation of different building blocks onto
either rim of the CD torus in a sequential and controlled manner, offering a unique
opportunity for structure-activity relationship and optimization studies.1,2
Both the charge
density and the hydrophobic-hydrophilic balance can be tuned in an overall architecture that is
inspired in that of the cationic lipids. We have now implemented this bidirectional diversity-
oriented concept for the construction of amphiphilic polycationic βCD “click clusters” (Figure
1) as a new family of discrete and well-characterized macromolecular nucleic acid vehicles.
The molecular construct benefits from the high yield of the “click” coupling, even in sterically
hindered environments,3 and the possibility to control the self-assembling properties of the
adducts, their ability to interact with pDNA, and the membrane-crossing and transfection
capabilities of the corresponding CD-pDNA complexes (CDplexes).
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Figure 1. Schematic representation of βCD-scaffolded amphiphilic polycationic “click clusters”. The rectangular boxes
account for additional spacer elements.
1 Díaz-Moscoso, A.; Balbuena, P.; Gómez-García, M.; Ortiz Mellet, C.; Benito, J. M.; Le Gourriérec,
L.; Di Giorgio, C.; Vierling, P.; Mazzaglia, A.; Micalli, N.; Defaye, J.; García Fernández, J. M. Chem. Commun. 2008, 2001-2003.
2 Ortega-Caballero, F.; Ortiz Mellet, C.; Le Gourriérec, L.; Guilloteau, N.; Di Giorgio, C.; Pierre Vierling, P.; Defaye, J.; García Fernández, J. M. Org. Lett. 2008, 10, 5143-5146.
3 Ortega-Muñoz, M.; Morales-Frutos, J.; Perez-Balderas, F.; Hernandez-Mateos, F.; Giron-Gonzalez, M. D.; Sevillano-Tripero, N.; Salto-Gonzalez, R.; Santoyo-Gonzalez, F. Org. Biomol. Chem. 2007, 5, 2291-2301.
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GLUTATHIONE RESPONSIVE POLYURETHANES AS POTENTIAL MATERIALS FOR BIOMEDICAL APPLICATIONS
M. Violante de Paz, Francisca Zamora, Juan A. Galbis
Departamento de Química Orgánica y Farmacéutica. Universidad de Sevilla.
C/ Profesor García González nº 2, 41012 Sevilla, Spain [email protected], [email protected], [email protected]
In this study, we have designed, synthesized and characterized a group of novel glutathione responsive copolymers with potential biomedical applications. A glutathione reactive monomer, 2,2’dithiodiethanol was incorporated into arabinitol-based polyurethanes in order to enhance the biodegradation properties of the new materials under physiological conditions. The diisocyanate monomer used, 1,6-hexamethylene diisocyanate (HMDI), has proved to be suitable for the synthesis of polyurethanes with low toxicity for humans and hence, for further uses as biomedical materials. The second diol monomer was a carbohydrate-based molecule, chosen between 2,3,4-tri-O-benzyl-L-arabinitol and 2,3,4-tri-O-methyl-L-arabinitol.
The polyurethanes were prepared with higher or equal proportion of the sugar-based monomer related to 2,2’dithiodiethanol. The copolymer compositions were studied by elemental microanalyses and 1H-NMR. It was verified the good agreement between the theoretical and the experimental compositions of the copolymers.
The macromolecules were fully characterised and their degradation properties under physiological conditions were tested. Those properties were compared with a model homopolymer, the new PU (DiT-HMDI) polyurethane. The homo- and copolyurethanes have proved to be biodegradable under physiological conditions. The kinetics of degradations do not only depend on glutathione reactive monomer ratio in the polymer but also on the crystallinity and the hydrophilic character of the final macromolecule. Some of the polymers suffered a reduction in their Mw of almost 80% in only three days.
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NEW AMPHIPHILIC GLYCOPOLYMERS BASED ON A POLYCAPROLACTONE-MALEIC ANHYDRIDE BACKBONE. CHARACTERIZATION BY 15N NMR AND USE
FOR THE COLLOIDAL STABILIZATION OF NANOPARTICLES.
Otman Otman,a* Paul Boullanger,a Dominique Lafont,a and Thierry Hamaideb
(a) Université de Lyon ; université Lyon 1 ; Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Chimie Organique 2 – Glycochimie, CNRS UMR 5246, CPE-Lyon. 43,
boulevard du 11 Novembre 1918, Villeurbanne, F-69622, France. *[email protected] (b) Université de Lyon ; université Lyon 1 ; Laboratoire des Matériaux Polymères et Biomatériaux (LMPB), Ingénierie des Matériaux Polymères, CNRS UMR 5627, ISTIL. 15 boulevard Latarjet,
Villeurbanne, F-69622, France.
Synthetic polymer-based nanoparticles able to encapsulate drugs receive considerable attention because of their potential use as controlled drug delivery systems. They represent attractive alternatives to conventional pharmaceutical applications such as reduced toxicity or improved efficacy. In addition, specific targeting may be offered by coating nanoparticles with oligo- or polysaccharide chains since the carbohydrate moiety plays an essential role in the molecular recognition process. Good bindings were reported for monosaccharide ligands; for instance, galactose residues are suitable ligands for hepatocytes[1] while mannose is used for nervous cells[2]. For instance, the chemical composition of the polymer matrix may affect the particle morphology because of thermodynamic interactions between the hydrophobic drug and the polymer. Size and colloidal stability are ensured by using surfactants. Nevertheless, the choice of the surfactants is restricted because of the numerous constraints in relation with their further use in pharmacy. For instance, triblock copolymers such as Pluronic® F-68 (PEO-b-PPO-b-PEO) are accepted by FDA and widely used in pharmaceutical formulations. Poly(ε-caprolactone) (PCL) which is a well known biocompatible and biodegradable polymer can advantageously replaces PPG chains as hydrophobic part. It may be reminded that PCL is widely used for the encapsulation of drugs in polymer matrices. PCL chains can be incorporated as side chains in a hydrophilic backbone, via the PCL macromonomer copolymerisation with maleic anhydride and N-vinyl pyrrolidone[3]. This paper reports on the synthesis and characterization of amphiphilic copolymers bearing carbohydrate and oligocaprolactone side chains, obtained via copolymerization of a PCL macromonomer and maleic anhydride (scheme). The grafting of carbohydrates with the functionnalized copolymer was ascertained by 15N NMR experiments. These copolymers were then used as surfactants for the stabilisation of PCL nanoparticles coated with carbohydrates on their surface and are to be used as targets for vectorisation.
H O O C
H O O CR
RO
O
H N
O
H N
O
O H
H O
O
O
R
RO O
O O O
N H 2H O
P C L
P C L
P C L
P C L
1 Y. Muraji, Y. Nakagawa, S. Yamane, S. Kawanami, T. Aoki, S. Saito, A. Ikai, Jpn. J. Appl. Phys. 2006, 45,
2298. 2 I. Galea Ian, K. Palin, T. A. Newman, N. Van Rooijen N, H. V. Perry, D. Boche, Glia 2005, 49, 375. 3 C. Iojoiu, D. Cade, H. Fessi, T. Hamaide, Polym. Int. 2006, 55, 222.
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P40
CHEMICAL MODIFICATION OF URONIC ACIDS AND OLIGOURONIDES UNDER MICROWAVE IRRADIATION IN SOLVENT FREE CONDITIONS
Stéphanie Rat,a José Kovensky,a Philippe Michaud,b Anne Wadouachia
(a) Laboratoire des Glucides UMR 6219 CNRS, Université de Picardie Jules Verne, 33 rue Saint-Leu,
80039 Amiens cedex, France (b) Laboratoire de Génie chimique et Biochimique, université blaise Pascal – Polytech Clermont
Ferrand, 24 rue des Landais, 63174 Aubière, France
In the 90’s, the concept of « Green Chemistry » was established. Since, research has grown with new technologies focused on reducing waste and energy use, using renewable resources and generating safe products.1 Solvent-free methods and microwave technology are especially adapted to this concept, . The short reaction times and expanded reaction range obtained by microwave assisted organic synthesis are suited to the increased demands in industry. Combined with microwave irradiations, solvent-free methods give then very efficient and clean reactions with noticeable improvement over classical methods.2
Glycosides of D-glucuronic acid are ubiquitous components of oligo- and polysaccharides of biological interests. First, glycosylation and/or esterification reactions of D-glucuronic acid (GlcA) catalyzed with various Lewis acids were studied under microwave irradiation and solvent-free conditions to access rapidly to modified uronate derivatives.3
Second, sulfatation reaction of uronic acids was realized in solventless conditions under microwaves irradiations and applied to oligoglucuronans of dp between 4 and 14. The sulfated oligoglucuronanes have been evaluated for their elicitor activity on grapevine.4 Oligosaccharides are biological activators capable to strengthen the endogenous defences of plants which can constitute an attractive alternative to current chemical methods.5,6
1 Anastas, P.T.; Warner, J.C. Green chemistry theory and practice, Oxford, Oxford university press, 1998, 135p.
2 Microwaves in Organic Synthesis (Ed: A. Loupy), Wiley-VCH, Weinheim, 2006. 3 Rat, S., Mathiron, D., Michaud, P., Kovensky, J., Wadouachi, A. Tetrahedron, 2007, 63, 12424-
12428. 4 FR Patent N° 08/01559-21.03.08 ”(1→4)-�-D-polyglucuronic acids, mixture and phytosanitary
products associated. Their use as elicitors and synthesis methodology”. 5 Aziz, A;, Heyraud, A., Lambert, B. Planta 2004, 218, 767-774. 6 Angelova, Z., Georgiev, S., Roos, W, Biotechnol; & Biotechnol. Eq. 2006, 20(2),72-83.
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AQUEOUS-PHASE EXTRACTION OF GLUCURONOXYLANS FROM CHESTNUT WOOD: NEW STRATEGY FOR LIGNIN OXIDATION USING PORPHYRIN OR
PHTHALOCYANINE IN H2O2 SOLUTIONS
Aline Barbat, Vincent Gloaguen* and Pierre Krausz
Université de Limoges, Laboratoire de Chimie des Substances Naturelles, UPRES EA 1069-GDR CNRS 3049, 123 rue Albert Thomas, LIMOGES 87060, France, * [email protected]
4-O-methylglucuronoxylan (MGX) is a common hemicellulose usually found in plant cell wall and which presents various biological properties1.
O
HOOH O
OHO
OH OOHO
OH OOHO
OH OOHO
OOHO
OHO
OMeO
HO
OOH
HOOC
n In wood, MGX is covalently linked to lignin and, for this reason, MGX extraction usually requires a preliminary chlorite delignification followed by treatment with a concentrated alkaline solution. This method is polluting, and not easily handled. In addition, it induces the complete deacetylation of MGX and a decrease of its degree of polymerization. In order to understand the role of MGX in the plant secondary cell wall organization, but also to encourage new ways of valorization, the development of greener alternative strategy of extraction is needed. To this aim, we propose an aqueous extraction procedure of MGX. Chestnut sawdust was first delignified by a radical reaction in water in presence of hydrogen peroxide and a sulfonated photosensitizer. The latter consisted in a porphyrin or a phthalocyanine, metalled with either iron or manganese. MGX were then extracted by hot-water. The protocol, reproduced with different time and temperature conditions, led to the selective extraction of homogeneous acetylated MGX with acceptable yields ranging from 4 to 14%.
N N
NN
SO3Na
SO3Na
NaO3S
SO3Na
SO3Na
SO3Na
NaO3S
N
N
N
N N
N
N
N
NaO3S
M
Porphyrins and phthalocyanines used in the process
M
M = Fe or Mn
1 Barbat, A., Gloaguen, V., Moine, C., Sainte-Catherine, O., Kraemer, M., Rogniaux, H., Ropartz, D.,
Krausz, P. J. Nat. Prod. 2008, 71, 1404-1409.
H2O2 Porphyrin or phthalocyanin
e [Porphyrin or
phthalocyanine] +·
Sawdust
Holocellulose
H2O
H2O
MGX
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P42
HYDROLYSIS OF SUCROSE OVER SULFONATED POLY(VINYL ALCOHOL)
D.S. Pito,a I.M. Fonseca,b A.M. Ramos,b J. Vital,b J.E. Castanheiroa*
(a) Centro de Química de Évora, Departamento de Química, Universidade de Évora, 7000-671 Évora, Portugal, * [email protected]
(b) REQUIMTE/CQFB, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Recently, biomass attracts much attention as a renewable feedstock due to its ‘‘CO2 neutral’’ impact on the environment. Sugars are key intermediates from biomass to chemicals, and conversion of sugars also requires a green process. Sucrose is widely present in the plant kingdom and constitutes the main carbohydrate reserve and energy source required in humans’ diets. The hydrolysis of sucrose allows its conversion into inverted sugars, i.e., glucose and fructose, which are widely used in the food industry. Enzymes were the main industrial catalysts used for the hydrolysis of sucrose, but they present different drawbacks, such as the production of waste, low thermal stability, and problems with separation and recovery of the enzyme from the product1. Heterogeneous catalysts may find an opportunity for replacing the enzyme catalyst. The hydrolysis of sucrose has been carried out over heterogeneous catalysts, such as, zeolites2, polystyrene with sulfonic acid groups3 and sulfonated mesoporous silicas4. Poly(vinyl alcohol) cross-linked with either sulfosuccinic acid or 5-sulfosalicylic acid was used as catalyst in the esterification of acetic acid with isoamylic alcohol5. In this work, we report the hydrolysis of sucrose over poly(vinyl alcohol) (PVA) with sulfonic acid groups. Influence of various reaction parameters, such as, concentration of sucrose, catalyst loading and temperature on activity of the most efficient catalyst was studied. PVA polymeric catalysts were prepared by dissolving PVA in water at 90 ºC, with the
appropriate amounts of sulfosuccinic acid, according to Rhim6 et al. The code PVA_x means a matrix containing x% of OH groups esterified. The catalytic experiments were carried out in a stirred batch reactor, at 80 ºC. In a typical experiment, the reactor was loaded with 100 mL of sucrose 0.6 M. Reactions were started by adding 0.511 g of catalyst. Fig. 1 allows to compare the catalytic activity of PVA_X, as catalysts, in the hydrolysis of sucrose, at 80 ºC. It was observed that when the cross-linking degree increases, the catalytic activity increases as well, due to the increased amount of sulfonic acid groups in the catalysts.
1 Corma, A., Iborra, S., Velty, A. Chem. Rev. 2007, 107, 2411-2502. 2 Moreau, C., Durand, R., Aliès, F., Cotillon, M., Frutz, T., Théoleyre, M., Ind. Crops Products 2000,
11, 237-242. 3 Nasefa, M. M., Saidia, H., Sennab, M. M. Chem. Eng. J. 2005, 108, 13–17. 4 Dhepe, P.L., Ohashi, M., Inagaki, S., Ichikawa, M., Fukuoka, A. Catal. Lett. 2005, 102, 163-169. 5 Castanheiro, J.E., Ramos, A.M., Fonseca, I.M., Vital, J. Appl. Catal. A. 2006, 311, 17-23. 6 Rhim, J. W., Park, H. B., Lee, C. S., Jun, J. H., Kim, D. S., Lee, Y. M., J. Memb. Sci. 2004, 238, 143-
151.
0
1
2
3
4
5
6
PVA_5 PVA_20 PVA_40
Act
ivity
x 1
03 (m
ol/h
.gca
t)
0
1
2
Act
ivity
(m
ol/h
.mm
ol S
O3H
)
Fig. 1. Hydrolysis of sucrose over poly(vinyl alcohol) with sulfonic acid groups, at 80ºC.
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P43
DEHYDRATION OF D-XYLOSE INTO FURFURAL BY SOLID ACIDS DERIVED FROM A LAYERED ZEOLITE
Sérgio Lima, Martyn Pillinger, Anabela A. Valente*
Department of Chemistry, University of Aveiro, CICECO, 3810-193 Aveiro,
Portugal,*[email protected] Furfural is a versatile, renewable chemical with a wide industrial application profile: for example as chemical feedstock for the production of furfuryl alcohol and for other 5-membered oxygen-containing heterocycles such as furan and tetrahydrofuran.1,2 Furfural may be obtained via acid dehydration of xylose. Most processes of furfural production employ mineral acids as catalysts, especially sulfuric acid, which leads to serious corrosion and safety problems, difficult catalyst separation from the reaction products, and excessive waste disposal.1 The use of conventional microporous zeolites as catalysts for xylose dehydration is compromised by the diffusion limitations inherent in the relatively narrow pore dimensions. One solution to this problem that has been developed during the last decade involves the delamination of layered precursors of zeolites. The idea is to obtain, in the limit, single crystalline sheets of zeolitic nature with all catalytically active sites being accessible to the reagent molecules. The obtained materials share the acid properties and (hydro)thermal stability of zeolites, but possess enhanced specific surface area and porosity as compared with the precursors, leading to improved diffusion and desorption of organic compounds, and lower rates of catalyst deactivation.
We studied the catalytic performance of several materials derived from a layered zeolite Nu(6)-1, prepared from the lamellar precursor Nu-6(1), namely alkali and proton-form Nu-6(2), and a material obtained after swelling/ultrasonication/calcination of Nu-6(1), in the liquid-phase cyclodehydration of xylose to furfural, at 170 ºC. The final material, with a specific surface area about seven times higher than that for proton-exchanged Nu-6(2), gave a reaction rate about two times higher than that for H-Nu-6(2), and could be recycled several times without loss of performance or Al leaching. The furfural yield after 4 h reaction was 47%, compared with 34% in the presence of an H-mordenite sample with Si/Al ~ 6.3
1 Zeitsch, K.J. The Chemistry and Technology of Furfural and Its Many By-Products, first ed., in:
Sugar Series, 2000, vol. 13, Elsevier, The Netherlands. 2 Chheda, J.N., Huber, G.W., Dumesic, J.A. Angew. Chem. Int. Ed., 2007, 46, 7164-7183. 3 Lima, S., Pillinger, M., Valente, A. A. Catalysis Communications, 2008, 9, 2144-2148.
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CATALYTIC DEHYDRATION OF D-XYLOSE TO FURFURAL
Anabela A. Valente*, Ana S. Dias, Sérgio Lima, Martyn Pillinger
Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal, * [email protected]
Furfural (1) is a key derivative for the production of a wide range of non-petroleum-derived chemicals. It can be made from agricultural raw materials and surpluses rich in pentoglycans, especially xylan, by aqueous acid treatment to hydrolyze the xylan to xylose (Xyl), with subsequent dehydration to 1. Established industrial processes for production of furfural use conventional mineral acids, such as sulfuric acid, which are corrosive, toxic, and difficult to handle and recover. We now report on the catalytic performance of several heterogeneous acid catalysts for the liquid-phase dehydration of Xyl to 1.
Heteropolyacids supported on mesoporous silicas gave yields in this reaction comparable with those obtained using H2SO4 under similar reaction conditions, but the supported heteropolyacids are partially leached into the aqueous phase during the reaction, compromising the catalyst’s reusability.
Sulfonic acid-functionalized ordered mesoporous silicas were found to effectively catalyse this reaction, using either dimethyl sulfoxide or a water-toluene mixture2 as the solvent. However, a limitation of these catalysts is that the thermal removal of coke from the surface of used catalysts requires heating above the thermal stability limit of the surface-bound alkylsulfonic groups. Bulk and mesoporous silica-supported (per)sulfated zirconia were also prepared with attention to the effect of aluminium incorporation. In general, these materials exhibited higher catalytic activity than sulfuric acid3. In the recycling experiments, these catalysts suffered sulfur leaching, but not always loss of activity.
A microporous niobium silicate, AM-11 was found to be more water-tolerant and could be reused without loss of activity or selectivity between recycling runs, yielding more 1 than HY zeolite or mordenite4. Mesoporous niobosilicates, Nb-MCM-41, possess higher initial activity than AM-11, but lower stability in recycling runs. Mesoporous aluminosilicates possess lower initial catalytic activity than Nb-MCM-41, but eventually lead to higher yields of 1, without significant loss of catalytic activity in recycling runs.
Crystalline layered metal oxide cation exchangers, such as titanates, niobates, and titanoniobates, are potentially strong solid acids when in the H+-form. However, the high charge density of the anionic sheets in these materials hinders the access of bulky substrate molecules to the acid sites. One approach to increase the specific surface area of these materials involves exfoliation, resulting in aggregates of nanosheets. These exfoliated materials are active, selective and stable catalysts, exhibiting higher performance than sulfuric acid and some zeolites5.
We thank FCT for financial support (project POCI/QUI/56112/2004), and for PhD (A.S.Dias) and post-doctoral (S.Lima) grants. 1 Dias A. S., Pillinger M., Valente A. A., Microporous and Mesoporous Materials 2006, 94, 214-225. 2 Dias A. S., Pillinger M., Valente A. A., J. Catal. 2005, 229, 414-423. 3 Dias A. S, Lima S., Pillinger M., Valente A. A., Catal. Lett. 2007, 114, 151-160. 4 Dias A. S., Lima S., Brandão P., Pillinger M., Rocha J., Valente A. A., Catal. Lett. 2006, 108, 179-186. 5 Dias A. S., Lima S., Carriazo D., Rives V., Pillinger M., Valente A. A., J. Catal. 2006, 244, 230-237.
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SYNTHESIS OF LEVULINIC ACID : A COMPARAISON BETWEEN PRESSURIZED BATCH AND REACTIVE EXTRUSION PROCESS
Pierre Ferchaud,a,c,* Hélène Ducatel,a Camille Viot,a Philippe De Braeckelaer,a Anne Wagner,b Maurice Essers,b c
(a) Centre de Valorisation des Glucides, 33 avenue Paul Claudel, 80480 Dury, FRANCE
(b) Syral, ZI portuaire, 67390 Marckolsheim, FRANCE (c) Laboratoire des glucides, UMR 6219, 10 rue Baudelocque, 80039 Amiens, FRANCE
*[email protected] Levulinic acid is small fatty acid having an γ-ketone function. The presence of these 2 functions makes the levulinic acid a highly versatile molecule that can be used, as a raw material, in many industrial applications, like resins, plasticizers, textiles, fuel-additives, coating or biodegradable herbicide.1 The main way of its synthesis is the degradation of sugars in an acidic media (Fig 1). Since 1870, many sugar sources have been studied, like starch, inulin or hexose, and many minerals or organics acids have been employed. But its development is slowed down because of high production costs, due to non-continuous processes and low yields.
OOH O
O
OH
OO
OH
O
OH OH
n
Levulinic Acid5-HMFSugar source
Industrial
applications
H+ H+
Fig 1. Major steps of the acidic synthesis of levulinic acid.
Based on the works of Hanna,2 our goal in this study is to compare the efficiency of 2 processes: pressurized batch reactor and reactive extrusion. The extruder can be considered as a green chemistry reactor, since it is a continuous process that can reduce the reaction time and the solvent consumption. We studied the extrusion of starch, dextrose and fructose at 180 °C in presence of sulfuric acid and we have compared these results with batch reaction at the same temperature and concentration of acid. This poster will present the advantages and the limitations of the reactive extrusion process, compared to the batch reaction.
1 Ghorpade, V. M., Hanna, M. A., Cereals Novel Uses and Process 1997, 49-55. 2 Cha, J. Y., Hanna, M. A., Industrial Crops and Products 2002, 16, 109-118.
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P46
CARBOHYDRATES EXTRACTION FROM AQUEOUS SOLUTIONS USING IONIC LIQUIDS
Andreia A. Rosatella,a* Luís C. Branco,b Carlos A.M. Afonsoa
(a)CQFM, Departamento de Engenharia Química e Biológica, Instituto Superior Técnico, Av. Rovisco
Pais, 1049-001 Lisboa, Portugal, *[email protected] (b) REQUIMTE/CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade
Nova de Lisboa, 2829-516 Caparica, Portugal
Ionic Liquids (ILs) are compounds that contain only ions and have a melting point below 100ºC. They are versatile compounds due to the possibility to tune the desired property such as polarity, conductivity, thermal and chemical stability, density, viscosity, melting point, and their solvent capability just by combining different anions and cations 1. Due to their capacity to dissolve a large amount of carbohydrates, ILs have been reported as solvents for carbohydrate chemistry2. The best result reported for the dissolution of glucose is butylmethylimidazolium chloride that can dissolve 145 mg of glucose per mL of IL3. We have studied the dissolution of glucose, fructose, lactose and sucrose in several ILs and shown that the solubility of glucose can be improved to 385.8 mg per g of IL, with tetra(2-methoxyethyl)dimethylguanidinium chloride4. In this study we also studied the anion effect and the influence of the water content in the glucose solubility on the IL. We have observed that some hydrophobic IL that are immiscible in water, can also dissolve low molecular carbohydrates, and are able to extract carbohydrates from an aqueous solution. Carbohydrates extraction from aqueous solutions has been reported using quaternary ammonium salts and lipophilic boronic acids5. Here we described a much simpler method for the extraction where a hydrophobic IL can extract directly the carbohydrate from an aqueous solution without the need of a surfactant, or a buffer solution in the aqueous phase. Several ILs (Figure) were tested for the extraction of glucose and mixtures of glucose/fructose, fructose/lactose and lactose/sucrose from an aqueous solution, in witch was observed a dependence of the partition with the IL.
Figure: Ionic Liquids used for the extraction of carbohydrates from aqueous solutions.
Acknowledgements: We would like to thank the financial support from Fundação para a Ciência e Técnologia (POCI 2010) and FEDER (ref.: SFRH/BD/28242/2006, PTDC/QUI/66826/2006 and PTDC/QUI/70902/2006). 1 J. Dupont, in Green Separation Processes: Fundamentals and Applications, ed. C. A. M. Afonso and
J. P. G. Crespo, Wiley-VCH, Weinheim, 2005. 2 R. M. Lau, F. van Rantwijk, K. R. Seddon and R. A. Sheldon, Org Lett, 2000, 2, 4189-4191; S. A.
Forsyth, D. R. MacFarlane, R. J. Thomson and M. von Itzstein, Chem Commun, 2002, 714-715. 3 Q. B. Liu, M. H. A. Janssen, F. van Rantwijk and R. A. Sheldon, Green Chem, 2005, 7, 39-42. 4 A. A. Rosatella, L. C. Branco, C.A.M. Afonso, article submited. 5 Aziz, H. A.; Kamaruddin, A. H.; Abu Bakar, M. Z. Sep. Purif. Technol. 2008, 60, 190.
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INFLUENCE OF ISOLATION METHODS ON PROPERTIES OF CHESTNUT STARCH
Paula M. Correia,a,* Maria L. Beirão-da-Costab
(a) Departamento de Indústrias Alimentares, Escola Superior Agrária do Instituto Politécnico de Viseu.
Quinta da Alagoa. Estrada de Nelas, 3500-606 Viseu. PORTUGAL. *[email protected]
(b) Departamento de Agro-Industrias e Agronomia Tropical, Instituto Superior de Agronomia da Technical University of Lisbon. Tapada da Ajuda, 1349-017 Lisboa. Portugal
Castanea sativa Mill. is an important agroresource in Portugal. The use of chestnut in human nutrition goes back to ancient times. The fruits are mainly composed by carbohydrates, with a small content of proteins and fats. The predominant carbohydrate is starch, 47%1. Starch can be extracted using different processes. Based on the simplicity, efficiency, quickness and safety questions four different laboratory scale methods were applied2,3. The methods involved centrifugation and sieving, but in a first step, in order to increase separation chemical or enzymatic treatments were applied. The four methods are identified as A: low deformation at alkaline pH2, B: high deformation in water2, C: low deformation with protease2 and D: alkaline pH using three sieves3. The isolated starches were analysed for: yield, moisture4, protein4, fat4, ash4 and amylose content5, starch purity6, morphology (SEM), damaged starch7,8, colour and viscoamylographic profiles. The results showed that the extraction methods induced differences in starch properties. In general, the amylose content is higher in isolated starch when compared to its content in raw material, the higher value being observed for starch isolated by C and D methods. The yield and starch purity were higher for method D (33.1% and 95.8%, respectively) and lower for method B. The damage starch content is higher, suggesting that starch is poorly resistant to any of the tested isolation procedures. SEM observations showed that isolated starches presented similar morphology but structure seems to be damaged. Starches presented higher L* and colour differences is very distinct. Pastes form D method presented higher peak consistency (1510 B.U.) and final consistency (1380 B.U.).Chestnut starch seems to be affected mainly by pH of the medium and not so much by physical forces. Two of the tested methods (C and D) were selected as the most promising ones. Method D was optimized by the RSM methodology using as independent variables centrifugation speed and time. Using the optimized conditions the use of an enzymatic pre-treatment (method C) was also tested. The extracted starch was evaluated for yield and purity. Optimised conditions were found to be: 2810 rpm/23 min using 540 units protease for enzymatic pre-treatment during 7-30 h. 1 Correia, P.; Beirão-da-Costa, M. J. Food Eng. 2009, 90, 325. 2 Lim, W. J.; Liang, Y. T.; Seib, P. A.; Rao, C. S. Cereal Chem. 1992, 69, 233. 3 Perez, E.E.; Bahnassey, Y. A.; Breene, W. M. Starch/Stärke. 1993, 45, 211. 4 AOAC. Official methods of analysis. 2000. 5 Juliano, B. O. Cereal Sci. Today. 1971, 16, 334. 6 ISO/DIS 10520, 1997. 7 AACC. Approved methods. 2000. 8 Hizukuri, S.; Takeda, Y.; Yasuda, M. & Suzuki, A.. Carbohydr. Res. 1981, 94, 205.
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ALGINATE AEROGELS AS ADSORBENTS OF POLAR MOLECULES FROM LIQUID HYDROCARBONS
Francesco Di Renzo,a,* Rosalia Rodriguez Escudero,a,b Mike Robitzer,a and Françoise Quignarda
(a) Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-ENSCM-UM1,
Matériaux Avancés pour la Catalyse et la Santé, ENSCM, 8 rue Ecole Normale, 34296 Montpellier Cedex 5, France, [email protected]
(b) Department of Chemical and Environmental Technology, Rey Juan Carlos University, 28933 Móstoles, Madrid, Spain
The preparation of alginate and alginic acid aerogels by supercritical CO2 drying provides solids with surface areas as high as 480 m2 g-1. This level of dispersion is retained when the aerogel is wetted by a non-polar solvent. The high surface area and the hydrophilic surface groups render alginate aerogels interesting adsorbents for traces of polar molecules in hydrocarbons. Aerogels of alginic acid and Ca-, Ba-, Co-, Ni-, and Cu-alginates have been tested as adsorbents for the separation of hexanol from dodecane. The equilibrium capacity was proportional to the surface area of the aerogel (Fig. 1) and corresponded to about one adsorbed molecule per uronic group exposed to the surface of the polymer fibrils. Concentration factors higher than 100 were observed. The adsorption site in the case of alginic acid aerogels has been modelled in analogy with the adsorption site on silica (another hydroxyl-rich adsorbent) and corresponds to the synergic interaction of the probe molecule with carboxyl and hydroxyl groups (Fig. 2). The interaction between the adsorbent and the polar probe molecule was stronger for alginate than for alginic acid aerogels. The strongest interaction was observed for the aerogels gelled by transition metal cations.
0
300
600
900
1200
0 5 10 15 20 25
hexanol in solution (µmol/ml)
adso
rbed
hex
anol
(µ
mol
/g)
Fig. 1. Adsorption isotherm of 1-hexanol on aerogels of Ca-alginate (empty circles), Ba-alginate (filled circles), and alginic acid (empty triangles). The lines are Langmuir plots of the data.
Fig. 2. Preferential site for localised adsorption of hexanol on mannuronic acid. Hydrogen bonds are formed with oxygens of two adjacent monomers.
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P49
WINE ADITIVATION WITH CORK
Luis Gil*, Carlos Pereira
INETI, Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal, *[email protected]
This study shows that when cork material gets in contact with wine, the elagitannins which exist in the cork material (namely one called vescalagin) react with the catechins present in the wine producing, among others, acutissimin-A, which is an anti-tumoural agent about 250 times more potent than one of the most common anti-cancer drug clinically used (VP-16). So, the contact of wine samples without the barrel winemaking stage was carried out with cork and acutissimina-A was detected.
This “vision” of the cork stoppers can be disadvantageous in relation to competitive products. So, a new vision of this natural stopper must be transmitted to consumers, this vision being the demonstration that cork has a positive influence in wine in opposition to synthetic closures (L. Gil, 2006)1.
The tests were carried out in duplicate with white and red wine. 16 samples of white and red wine which have contacted with cork or oak during 1 week and 2 months. Samples of white and red wine which have contacted cork during 30 min and 150 min were also analysed as well as 2 samples of red wine which have contacted with oak during 150 min. Acutissimin-A was detected in all the samples when wine contacted cork.
The organoleptic properties were also evaluated (aroma, taste and colour). It was a “blind” tasting, always including non modified wine among the tested wines. Organoleptically this additivation works better with white wines.
With this study it can be concluded that the contact of wine with a cork granulate affects positively some wines, namely for wines not aged in oak barrels and mainly white wines.
As the best results were achieved with wine tasting just after cork contact, this should be considered in wine treatments. However, even for these very short contact periods, there is acutissimin A formation, and the wine is enriched with this antitumour agent.
These results lead to a patent for wine additivation.
1 Gil L., 2006. A cortiça e o vinho. Ed. CEDINTEC/ INETI, Lisboa
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P50
CARBOHYDRATE-BASED LIQUID CRYSTALS: SYNTHESIS AND THERMOTROPIC BEHAVIOUR OF NEW MULTIFUNCTIONAL
SYSTEMS CONSTRUCTED FROM CMGL SYNTHONS
Fahima Ali Rachedi,a,b,c Stéphane Chambert,a,b Stephen J. Cowling,d John W. Goodby,d and Yves Queneaua,b
(a) INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne.
[email protected] (b) CNRS, UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires,
Université Lyon 1 ; INSA Lyon ; CPE Lyon. (c) Laboratoire de Chimie Organique Appliquée, Université Badji-Mokhtar, BP 12, 23000, Annaba,
Algérie. Département des Sciences, Centre Universitaire Souk-Ahras, 41000, Souk-Ahras, Algérie. (d) Department of Chemistry, The University of York, York, YO10 5DD, UK.
Glycolipids are molecules which have properties associated with a wide range of applications, from surfactants to biologically relevant molecules, notably with respect to cell membrnaes.1 Our current interests lie in the synthesis and study of the thermotropic liquid-crystalline behaviour of a variety of new synthetic glycolipids. Based on the use carboxymethyl glycoside lactones,2 a first series of glycosteroids (Structure I) were prepared. Although, due to their lack of flexibility, high melting points, limited LC temperature range, and thermal degradation of their liquid crystalline phases were observed.3 Here, we describe the synthesis of new multifunctional systems (Structure II, bearing a spacer between the carbohydrate and the steroid moieties, as well fatty chains of different length on the position 2 of glucose or cellobiose), which exhibited significantly improved liquid crystalline stability.
O
OR1OHO
OH
OO
NH
O
ONH
R2
OHOHO
HO
OH
R2= n-C8H17 or n-C12H25 or n-C16H33
R1= H orOHOHO
OH
OHO
NH
OIII
1 Goodby, J.W., Görtz, V., Cowling, S.J., MacKenzie, G., Martin, P., Plusquellec, D., Benvegnu, T.,
Boullanger, P., Lafont, D., Queneau, Y., Chambert, S., Fitremann, J. Chem.Soc. Rev. 2007, 36, 1971-2032.
2 Trombotto, S., Danel, M., Fitremann, J., Bouchu, A., Queneau, Y.; J. Org. Chem. 2003, 68, 6672-6678; Cheaib, R., Listkowski, A., Chambert, S., Doutheau, A., Queneau, Y. Tetrahedron: Asymmetry 2008, 19, 1919–1933.
3 Chambert, S., Cowling, S. J., Mackenzie, G., Goodby, J. W., Doutheau, A., Queneau, Y. J. Carbohydr. Chem. 2007, 26, 27-39.
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P51
SYNTHESIS AND PROPERTIES OF NEW CARBOHYDRATE BASED FLUORESCENT PROBES FOR NON-LINEAR OPTIC MEMBRANE IMAGING
S. Chambert,a,b,* R. Cheaib,a,b C. Barsu,c Y. Bretonnière,c O. Maury,c A. Girard-Ergot,b,d
L. Blum,b,d C. Andraudc and Y. Queneaua,b
(a) INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne.
[email protected] (b) CNRS, UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université
Lyon 1 ; INSA Lyon ; CPE Lyon. (c) Laboratoire de Chimie de l’ENS de Lyon, UMR 5182 CNRS - ENS, 46 allée d’Italie, 69364 Lyon,
France (d) Laboratoire de Génie Enzymatique et Biomoléculaire, Bât CPE, 69622 Villeurbanne.
New membrane glycoprobes designed for two-photon excited fluorescence (TPEF) and second harmonic imaging microscopy (two phenomena for imaging different biological systems1 with promising applications for the measurement of membrane potential of neuronal activity2) have been prepared and their ability to insert into membranes was investigated. The mono- or disaccharidic carbohydrate entities were grafted on the chromophore by reaction of the aniline system with carboxymethylglycoside lactones (CMGLs).3 The quantum yields and solvatochromism of the obtained amphiphilic probes confirmed their fluorescence efficiency and structure property relationships have also been studied by Langmuir film balance technology on phosphilipidic monolayers. The obtained glycoprobes exhibit satisfactory water solubility, are able to generate TPEF and GSH signals and show a longer membrane residence time compared to commercially available dyes (ANEP type probes), proving that the intense polarity of the sugar moiety efficiently maintain the probe within the membrane.
OROHO
OH
HO
OO
N
NH
NH
OROHO
OH
HO
OO N
ON
ON
R'
R'
R'
R'
two-photon fluorescencesecond harmonic generationsolubilityamphiphilicity good membrane insertionimproved membrane residence timeR = H
R = β-Gal
R'= C2H5R'= C8H17
1 Denk, W., Stricker J.H., Webb, W.W. Science, 1990, 248, 73 -76; Sacconi, L., Dombeck, D. A.,
Webb, W.W. Proc. Natl. Acad. Sci. USA, 2006, 103, 3124-3129. 2 Bouevitch, O., Lewis, A., Pinevsky, I., Wuskell J.P., Loew, L.M. Biophys. J., 1993, 65, 672-xx; Mertz,
J.. Curr. Opin. Neurol., 2004, 14, 610-616. 3 Trombotto, S., Danel, M., Fitremann, J., Bouchu, A., Queneau., Y. J. Org. Chem., 2003, 68, 6672-
6678; Le Chevalier, A., Pierre, R., Chambert, S., Doutheau, A., Queneau., Y. Tetrahedron Lett., 2006, 47, 2431-2434; Chambert, S., Cowling, S. J., Mackenzie, G., Goodby, J. W., Doutheau, A., Queneau Y. J. Carbohydr. Chem., 2007, 26, 27-39.
136
P52
SYNTHESIS AND RAFT POLYMERIZATION OF NEW ACRYLAMIDE BASED GLYCOMONOMERS
Ouaiss Abdel Kader,a,b,c Julien Bernard,c Stéphane Chambert,a,b Sylvie Moebs,a,b,*
Etienne Fleury,c Yves Queneau,a,b
(a) INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne (b) CNRS, UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires,
Université Lyon 1 ; INSA Lyon ; CPE Lyon, *[email protected] (c) INSA Lyon, UMR 5223, Laboratoire de Matériaux Macromoléculaires, Villeurbanne
Glycopolymers are synthetic macromolecules containing several saccharide motifs as pendant or terminal functional groups. Due to the specific interactions between sugars and cell surface receptor proteins (lectins), glycopolymers are potentially useful materials for applications such as targeted drug delivery, biosensors and protein purification. Herein we present the evaluation of new hydrophilic glycomonomers in radical polymerization by using the Reversible Addition-Fragmentation chain Transfer (RAFT) approach1. The RAFT polymerization is a reliable method for the direct synthesis of well-defined glycopolymers in aqueous media, without the need to resort to protective group chemistry2. The synthesis of the monomers is based on the nucleophilic opening of carboxymethyl glycoside-lactones (for example CMG-L 1)3. The lactone 1 was used as starting material for the synthesis of the glucoside-based acrylamide 2 obtained in four steps. The kinetics of polymerization was monitored by 1H NMR. Gel permeation chromatography highlighted an increase in molecular weights with conversion and narrow polydispersity index (1.1-1.3) consistent with a controlled polymerization process. Through the use of variable [2]/[RAFT] ratio, poly (1-NH2-CH2-NH-AAGlc) 3 with a number-average degree of polymerization (DPn) in the range of 50-400 were synthesized. Other bi-functionalized monomers have been prepared by selective introduction of a functional group on the position 2 or 6.
HO S S
O S
OOH
HOOHO
OH
NH NH
O
O
n
HO S S
O S
+ACPA
H2O/MeOH 5/1, 70°C
OHOHO
OHO
OH
NH
HN
O
O 31
OAcO
AcOO
OAc
O
O 2
1 Lowe, A. B.; McCormick, C. L. Prog. Polym. Sci. 2007, 32, 283-351; Bernard, J.; Hao, X. J.; Davis,
T. P.; Barner-Kowollik, C.; Stenzel, M. H. Biomacromolecules 2006, 7, 232-238. 2 Spain, S. G.; Gibson, M. I.; Cameron, N. R. J. Polym. Sci. PartA : Polym. Chem. 2007, 45, 2059-
2072; Ladmiral, V.; Melia, E.; Haddleton, D. M. Eur. Polym. J. 2004, 40, 431-449. 3 Trombotto, S.; Danel, M.; Fitremann, J.; Bouchu, A.; Queneau, Y. J. Org. Chem. 2003, 68, 6672-
6678.
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P53
PHOTOSENSITIZERS GRAFTED ON CELLULOSE FABRICS: NEW PHOTOBACTERICIDAL MATERIALS
Cyril Ringot, Vincent Sol,* Robert Granet, Pierre Krausz
Université de Limoges, Laboratoire de Chimie des Substances Naturelles, UPRES EA 1069-GDR
CNRS 3049, 123 avenue Albert Thomas, 87060 Limoges, France - *[email protected]
Nosocomial infections have become a major concern. The appearance of multi-resistant bacteria (e.g. Staphylococcus aureus and Escherichia coli strains) have complicated this problem urging that new antibacterial approaches be developed. To this purpose, new materials possessing bactericidal properties (made of glass, plastic or textile), have been designed. Porphyrins are molecules of considerable interest due to their ability to act as photosensitizers when irradiated with visible light and recent studies have shown that porphyrins could be used in PACT (Photodynamic Antimicrobial ChemoTherapy). Two porphyrin-grafted antimicrobial textiles have been obtained from a cotton fabric: product 1, containing a neutral porphyrin bound to cellulose by the means of a “Click-Chemistry” reaction and product 2, in which a sulfonated porphyrin has been linked to cellulose by reaction with 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride).
N
NH
NH
N
SO3Na
NaO 3S SO3Na
NHN
NN
O
HO
O OH
O
OH
OH
O
OHOH
O ** n
O OH
O
OHO
OHOH
O **
N
NN
OH
O
N
N
N
N
CH3
H3C CH3
Zn
n
Antibacterial
surfaces
O
N
N
N
N
CH3
H3C CH3
Zn
CH
O O-
O
O-
O-
O
O-
O-
O-
O **
n
Cellulosic fabrics
O OR
O
OR
OR
O
OROR
OR
O **
n
O HO
O
OH
OH
O
HOOH
OH
O **
n
with R = OH or N3
CBr4-PPh3-NaN3 NaOH
H2N
N
NH
NH
N
SO3Na
NaO3S SO3Na
Cu(OAc)2
Na ascorbateN
N
N
Cl
ClCl
1 2Cellulose grafted with neutral
porphyrinCellulose grafted with anionic
porphyrin
Irradiated with visible light, these materials displayed a sensible antibacterial activity against two representative strains, Klebsellia pneumoniae and Staphylococcus aureus.
138
P54
ENZYMATIC POLYESTERIFICATION REACTIONS OF αααα-HYDROXY DICARBOXYLIC ACIDS
M. Gracia García-Martín,* E. Benito and Juan A. Galbis
Department of Organic and Pharmaceutical Chemistry, University of Seville,
41071 Seville (Spain). [email protected]
Carbohydrates are an important source of building blocks for the synthesis of biodegradable polymers, especially for biomedical applications because of their inherent properties of biocompatibility and biodegradability. Hydrophilic polymers are biodegradable and they are presently incorporated into the design of a rich variety of biomedical and pharmaceutical products. Among the different natural sources of hydrophilic monomers, carbohydrates stand out as highly convenient raw materials because they are inexpensive, readily available, and provide great stereochemical diversity. Carbohydrate-based polymers such as polyamides, polyesters, polyesteramides, polycarbonates, polyurethanes…, have been prepared by polycondensation reactions but such reactions required the preparation of the corresponding active monomers having the secondary hydroxyl groups O-protected mainly as methyl ethers.1 Final removal of the O-protecting groups from the polymers made difficult the availability to the corresponding hydrophilic polymers.
Some efforts have been made in order to obtain hydrophilic polyesters from carbohydrates. Takasu et al. studied the chemoselective dehydration polycondensation reactions of dicarboxylic acids including L-malic and L-tartaric acids with 1,9-nonanediol, at room temperature in the presence of rare-earth trifluoromethanesulfonate.2 Gross et al. prepared polyesters via a biocatalyzed regioselective polycondensation of adipic acid with 1,9-nonanediol and alditols using Candida antarctica lipase B (CALB) but they did not explain the percentage of alditol that was incorporated into de polymer chains.3
We now present some preliminary results on the enzymatic polyesterification reactions of L-tartaric and L-malic acids with 1,9-nonanediol and alditols. Neither of the functional groups of these starting monomers were previously activated nor protected, and the reactions were conducted in the presence of CALB. The reaction of L-tartaric acid with 1,9-nonanediol gave polyesters with Mn 21,000-23,000 and polydispersities in the range 1.4-1.8. Instead, L-malic acid gave lower Mn such as 4,500-7,800 and polydispersities of 1.6-2.0. Reactions were also conducted adding alditols as D-sorbitol and D-mannitol in the ratio dicarboxylic acid:1,9-nonanediol:alditol 1:08:0.2, and 1:0.5:05. Preliminary experiences showed the best results with L-tartaric acid and D-mannitol, what could explain certain stereoespecificity of the enzyme on these substrates.
1 Galbis, J. A., García-Martín, M. G. Sugars as Monomers. In: A. Gandini, M. N. Belgacem, Eds. Monomers, Oligomers, Polymers and Composites from Renewable Resources. Elsevier, Amsterdam, 2008. (Chapter 5). pp. 89-114.
2 Takasu, A., Shibata, Y., Narukawa, Y., Hirabayashi, T. Macromolecules 2007, 40, 151-153. 3 Hu, J., Gao, W., Kulsherstha, A., Gross, R. A. Macromolecules 2006, 39, 6789-6792.
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P55
NEW XYLO-OLIGOSACCHARIDES PRODUCED FROM CORN COBS BY ENZYMATIC HYDROLYSIS
Susana Marques, Andreia Dias, Francisco M. Gírio, and Patrícia Moura*
Departamento de Biotecnologia, INETI, Estrada do Paço do Lumiar, 22, 1649-038 Lisboa, Portugal,
Lignocellulosic materials are abundant, renewable and of relatively low cost, which confers them the status of economically attractive biomass substrates within a biorefinery scope. In the case of corn, approximately 50 percent of the weight of the total plant (stalk, leaf, cob, and husk) is residue left after harvest to maintain soil fertility or used to produce forage to animal fed. The cob is a hemicellulose-rich material, where xylan represents in average 50% of the cell wall polysaccharides. The water-soluble heteroxylan component of corn cobs (CC) was reported to exhibit significant immunomodulating properties1 and xylo-oligosaccharides (XOS) produced by hydrothermal treatment of CC demonstrated prebiotic potential2.
In this work, tailor-made xylo-oligosaccharides were obtained from CC by controlled enzymatic hydrolysis. Commercial enzyme preparations, exhibiting different levels of xylanolytic activities, namely endo-xylanase, β-xylosidase, acetyl esterase and arabinofuranosidase activities, were used for CC hydrolysis. On a first set of assays, Multifect Xylanase (Genencor) was selected, based on XOS production yield and minor monosaccharides concentrations. Following process optimization, 6.2 g of XOS was obtained from 100 g of xylan on CC, by applying Multifect Xylanase on a dosage of 500 U/g xylan. The characterization of the produced XOS, in terms of molecular size distribution, gave rise to two peaks, corresponding respectively to smaller degrees of polymerisation (DP), estimated on a range of DP 2 – 4, and to a higher DP range, with DP between 4 and 18. These longer XOS (98% of the mixture) possess a molecular size very different from commercially available XOS, a feature which might grant them unique prebiotic properties.
1 Ebringerová, A., Hromádková, Z. Int. J. Biol. Macromol. 1995, 17, 327-331. 2 Moura, P., Cabanas, S., Lourenço, P., Gírio, F.M., Loureiro-Dias, M.C., Esteves, M.P. LWT – Food
Science and Technol. 2008, 41, 1952-1961.
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P56
XYLO-OLIGOSACCHARIDES FROM LIGNOCELLULOSIC WASTES: TOWARDS A SYMBIOTIC PREPARATION WITH Bifidobacterium adolescentis
Patrícia Moura,a,* Patrícia Gullón,b Juan Carlos Parajó,b Francisco M. Gírioa
(a) Departamento de Biotecnologia, INETI, Estrada do Paço do Lumiar 22, 1649-038 Lisboa, Portugal;
(b) Departamento de Engenharia Química, Universidade de Vigo (Campus Ourense), As Lagoas, 32004 Ourense, Espanha. * [email protected]
Rice husks (RH) and corn cobs (CC) are two important sources of lignocellulosic materials available in large quantities and traditionally oriented for low value-added applications, e.g. as admixtures in animal feed. Under the framework of a lignocellulosic feedstock biorefinery, RH and CC can be used to produce bio-products of increased commercial value, such as prebiotic non digestible oligosaccharides, which include xylo-oligosaccharides (XOS).
In this work, the in vitro fermentability of RH XOS by probiotic bacteria was tested and compared with previous results obtained from CC XOS1. The RH liquors were produced by autohydrolysis and submitted to nanofiltration and enzymatic hydrolysis in order to obtain XOS with an average degree of polymerisation (DP) range of 2 - 6. The RH XOS were examined as carbohydrate source to promote the growth of Bifidobacterium adolescentis, B. breve, B. infantis and B. longum. The growth rate of B. adolescentis on RH XOS was higher than the ones determined for the other probiotic bacteria, corroborating the results obtained with CC XOS. The percentage of total RH XOS consumption by B. adolescentis was 77% after 24 h, the highest percentage of utilization corresponding to xylotriose (90%), followed by xylobiose (84%), xylotetraose (83%), and xylopentaose (71%). These results can be exploited with the view of combining short-chain XOS produced from lignocellulosic by-products with B. adolescentis, foreseeing a potential symbiotic preparation.
1 Moura, P., Barata, R., Carvalheiro, F., Gírio, F.M., Loureiro-Dias, M.C., Esteves, M.P. LWT – Food Sci. Technol. 2007, 40, 963-972.
141
P57
ANALYSIS OF OLIGOSACCHARIDES BY CAPILLARY-SCALE HIGH-PERFORMANCE ANION-EXCHANGE CHROMATOGRAPHY WITH PULSED
AMPEROMETRIC DETECTION (CHPAEC-PAD) AND ON-LINE ELECTROSPRAY-IONIZATION ION-TRAP MASS SPECTROMETRY (CHPAEC-ITMS).
C Bruggink,a,c CAM Koeleman,a V Barreto,b Y Lui,b C Pohl,b A Ingendoh,d M Wuhrer,a
CH Hokke,a AM Deeldera
(a) Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
(b) Dionex Corporation, Sunnyvale, California, USA (c) Dionex BV, Breda, The Netherlands
(d) Bruker Daltonik GmbH, Bremen, Germany High-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) is an established technique for the selective separation and analysis of underivatized carbohydrates. The miniaturization of chromatographic techniques by means of capillary columns, and on-line coupling to mass spectrometry are critical to the further development of glycan analysis methods that are compatible with the current requirements in clinical settings. A prototype system has been developed based on a Dionex BioLC equipped with a microbore gradient pump and a PEEK flow splitter, a FAMOS micro autosampler, a modified electrochemical cell for on-line capillary PAD and a capillary column (380 µm i.d.) packed with a new type of anion-exchange resin. This system operates with a sensitivity in the low fmol range. In addition, an on-line capillary desalter has been developed to allow direct coupling to a Bruker Esquire 3000 ion-trap mass spectrometer with an electrospray ionisation interface (ESI-IT-MS). Both systems have been evaluated using standard oligosaccharides as well as urine from children with various lysosomal oligosaccharide storage diseases. Our data indicate that the robust and selective anion-exchange system in combination with ESI-IT-MS for structure confirmation and analysis provides a powerful platform which is complementary to existing nano-/capillary LC-MS methods for analytical investigations of oligosaccharides from biological samples.
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P58
LOW MOLECULAR WEIGHT OLIGOSACCHARIDES: STUDIES ON MOLECULAR MOBILITY OF AMORPHOUS PHASE AND ON THE ENERGETICS OF
CRYSTALLINE FORM.
Susana S. Pinto,a,* Hermínio P. Diogo,b Joaquim J. Moura Ramosa
(a) Centro de Química-Física Molecular and IN-Institute of Nanoscience and Nanotechnology, Instituto
Superior Técnico, Universidade Técnica de Lisboa, 1049-001 Lisboa, Portugal. (b) Centro de Química Estrutural do Instituto Superior Técnico,
Av. Rovisco Pais, 1049-001 Lisboa, Portugal, * [email protected]
Carbohydrates are the main source of energy in cells, and therefore they are present in many organisms, playing an important role in their biological processes. Besides providing nutrition to living organisms, many sugars share other important functions. For example, they are use as raw materials in industrial fermentations, amorphous carbohydrates are often employed in the preservation of biological molecules, like proteins, used in pharmaceutical, cosmetic, and food industries to effectively encapsulate, stabilize, and ultimately control the release of labile active materials (e.g. drug delivery). On the other hand, crystalline carbohydrates are often used in the pharmaceutical formulations to improve stability and increase their shelf life. Despite the success revealed in different fields some sugars, like sucrose, trehalose and raffinose, occupy an important position in the metabolism of anhydrobiotic organisms. Nevertheless, the mechanism through which these sugars assist to protect the integrity of such entities is not yet fully understood. In addition, this ability is believed to be, at least partially, a consequence of two intrinsic factors: their high hydrogen–bonding ability and their relative easy tendency to form a glassy state.
Despite the frequent use of sugars as protecting agents, little is known about the slow molecular mobility, especially in the amorphous phase. Additionally, experimental values for the standard enthalpy of formation in the condensed phase, and the enthalpy of solution of these low molecular weight oligosaccharides are very limited, despite the usefulness of these thermodynamic quantities in the context of the energetic balances, ranging from the energy sequence in animal metabolism to the industrial production of raw materials. Most of the thermodynamic data available are old and part of them presenting low accuracy.
In this context, the study of the evolution of the molecular mobility, from high temperature down to the glassy state, is a relevant aspect related to the biopreservation skill. On the other hand, the lack of recent and principally accurate calorimetric experimental values is one of our motivations to initiate this project.
In this communication we will present studies involving slow molecular mobility in low molecular weight carbohydrates, in the amorphous form, by the dielectric technique of Thermally Stimulated Depolarization Currents (TSDC). The glass transition of these molecules is also characterized by Differential Scanning Calorimetry (DSC). Values for the activation enthalpies of the structural relaxation at Tg, Ea(Tg), and for the fragility index, m (Angell scale) will be determined from both studies. In addition, some thermochemical data, and the corresponding uncertainties, obtained from combustion calorimetry and solution calorimetry will be given. These values are convenient for an accurate development of an energetic balance where carbohydrate molecules are included.
Acknowledgements: A grant from Fundação para a Ciência e a Tecnologia is gratefully acknowledged by S. S. Pinto.
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P59
CARBOHYDRATES FROM BIOMASS AS A SOURCE OF BIOETHANOL
N. Gil,a F.C. Domingues,a,b M.E. Amaral,a,c A.P. Duartea,c,*
(a) Research Unit of Textile and Paper Materials, Universidade da Beira Interior,
6201-001 Covilhã, Portugal (b) Departament of Chemistry, Universidade da Beira Interior, 6201-001 Covilhã, Portugal
(c) Departament of Paper Science and Technology, Universidade da Beira Interior, 6201-001 Covilhã, Portugal
Production of ethanol (bioethanol) from biomass is one way to reduce both consumption and depletion of fossil fuels and environmental pollution. The cost of bioethanol production from lignocellulosic material is relatively high when based on current technologies, and the main challenges are the low yield and high cost of the hydrolysis process. The bioconversion of cellulose and hemicelluloses to monomeric sugars, for example carbohydrates with five and six carbons, is harder to accomplish than the conversion of starch, presently used for bioethanol production. Processing of lignocellulosics to bioethanol consists of four major unit operations: pretreatment, hydrolysis, fermentation and distillation. The step of pretreatment is the most important in bioconversion of lignocellulosics to bioethanol, the goal of any pretreatment technology is to alter or remove structural and compositional impediments to hydrolysis in order to improve the rate of enzyme hydrolysis and increase yields of fermentable sugars from cellulose or hemicelluloses.
The basic structure of all lignocellulosic biomass consists of tree basic polymers: cellulose, hemicelluloses and lignin. Cellulose fibers comprise 40-50 wt% of dry wood, hemicelluloses and lignin usually account for 25-35% of dry wood. Hemicelluloses are mixture of various polymerized monosaccharides such as glucose, mannose, galactose, xylose, arabinose and others. Xylose is the predominant pentose sugar derived from the hemicelluloses.
In the present work, the optimization of dilute acid pretreatment conditions of two species from forest biomass, namely Cytisus striatus (broom) and Cistus ladanifer (rock-rose), was studied with the purpose of ethanol production. The carbohydrates of the biomass samples were characterized after and before pretreatment by HPLC, as well as the filtrates from pretreatments. These filtrates were also characterized concerning the total reducing carbohydrates by the dinitrosalicylic acid (DNS) method. The composition of the two shrub species used in this study is present in Table 1.
Table 1. Biomass chemical composition (on an oven-dry basis).
Species Extractives
[%] Ash [%]
Insoluble lignin
[%]
Soluble lignin
[%]
Total lignin
[%]
Glucose [%]
Xylose [%]
Total sugars
[%] Stalks without
bark 1.8 0.8 23.0 1.9 24.9 - - -
Rock-rose Whole planta 7.4 3.1 32.0 2.2 34.2 33.1 15.9 49.0
Stalks without
bark 3.4 0.6 22.0 2.1 24.1 - - -
Broom Whole planta 4.7 0.8 22.4 2.3 24.7 45.9 19.5 65.4
a Wood, bark and leaves.
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SUGARCANE MOLASSES AS A LOW-COST STRATEGY TO IMPROVE STABILITY OF ANAEROBIC TREATMENT OF A PULP MILL EFFLUENT
Flávio Silvaa*, Marta Barbosaa, Helena Nadaisa, António Pratesb, Luís Arrojaa, Isabel Capelaa
(a)Departamento de Ambiente e Ordenamento, Universidade de Aveiro, Campus Universitário de
Santiago, 3810-196 Aveiro, Portugal *[email protected] (b)Caima – Indústria de Celulose, S.A., Constância-Sul, 2250-058 Constância, Portugal
The pulp industry is responsible for large discharges of highly polluted effluents, whose main characteristics are their high chemical oxygen demand (COD) and toxicity in the receiving environment. In sulphite pulping process, the wood cooking liquor (red liquor) is condensed in an evaporator system for chemicals reuse. The resulting liquid current (evaporator condensate, EC) contains mainly acetic acid (up to 80% of total organic matter content), making it suitable to be treated by an anaerobic reactor. However, it also contains high concentrations of sulphur compounds (namely SO2 and SO4
2-) that are reduced to sulphide under anaerobic environments. Free sulphide has been widely reported as inhibitory to mixed cultures of microorganisms. Furthermore the EC to be treated may accidentally carry high amounts of cooking liquor, when the evaporator system is washed. The red liquor has a very high organic matter content caused by the presence of ligno-sulphonates, dissolved lignin and other wood extractives, in addition to all EC components. In this situation, a further inhibition is often observed in the anaerobic reactor as the anaerobic biomass is not conveniently adapted to these recalcitrant materials, thus resulting in expensive treatment inefficiency.
This work presents a low-cost strategy to reduce imbalances by adding sugarcane molasses to the anaerobic reactor. Molasses is a by-product of sugar refinery and provides an external carbon source to the biological process. Batch experiments were performed to investigate the biodegradability and methanogenic potential of EC containing molasses addition at different ratios. The results showed maximum biodegradability at substrate concentrations lower than 2 g COD L-1 and for the highest molasses addition. In turn, methane production increased with substrate concentration increase. A kinetic study permitted the fitting of substrate uptake profiles to the Haldane model, which emphasised inhibition due to the substrate itself. Based in the best conditions achieved with the batch experiments, semi-continuous assays were performed to assess the feasibility of molasses addition on EC biodegradation, either under normal treatment conditions or under severe toxicity scenarios when red liquor is added. Results showed that the reactor containing molasses addition achieved higher stability when comparing with control reactor without molasses addition. The higher stability was noticed by higher organic matter removal capacity (from 52 to 77%), methane production increase (from 460 to 1650 mL d-1), and lower accumulation of intermediates. However, the reactor containing molasses addition accumulated higher molecular weight organic acids (propionic).
The results highlighted the beneficial effect provided by a small addition of molasses, which permits the increasing of the treatment performance and ensures a better acclimation of the biomass to organic and toxic shocks at full-scale operation. Hence molasses addition may be regarded as a low-cost operational strategy as it avoids the need for removal of sulphur compounds prior to the anaerobic treatment. Addition of molasses has been adopted in the full-scale plant, which permitted to achieve higher stability and performance.
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TREATMENT OPTIMIZATION OF RAW CANE SUGAR REFINING EFFLUENT
S. M. Nunes,a,* H. M. Pinheirob, M.T. Duartea, J. C. Bordado,c V. M. Vicentea
(a)DAI, Sociedade de Desenvolvimento Agro-Industrial SA, Monte da Barca, 2104-909 Coruche, Portugal, *[email protected]
(b)IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, Av. Rovisco Pais,1049-001 Lisboa, Portugal
(c)Department of Chemical and Biological Engineering, IBB, Instituto Superior Técnico, Av. Rovisco Pais,1049-001 Lisboa, Portugal
The aim of this work was to optimize the treatment of effluents coming from the refining of raw cane sugar, in the Wastewater Treatment Plant (WWTP) of DAI, SA, previously designed for the treatment of sugar beet processing wastewater with a continuous activated sludge reactor. The performance of activated sludge collected in the full-scale plant was analysed, with the original sugar beet effluent and with the effluents received from the refinery. The experimental system was constructed at laboratory/pilot scale (5 L working volume) and comprised two reactors, namely A and B, running in parallel. The behaviour of the full-scale activated sludge was simulated in Sequencing Batch Reactors (SBR) with permanent aeration and agitation. Effluents fed to these reactors were collected from the feed pipe of the WWTP. Inoculum biosludge was collected from a purge taken from the recycle stream in the WWTP. In reactor B, phosphogypsum waste was added, as a cheap source of phosphorus, for evaluation as a possible alternative to phosphoric acid supplementation. Values of chemical oxygen demand (COD) and total/volatile suspended solids (TSS/VSS) were monitored at different stages of the SBR cycle, for a period of 3 months, and used for performance calculations and estimation of kinetic and yield parameters. COD removal performance and the parameters affecting it were analysed. Specific organic loading values were calculated (Figure 1) in order to assess the effect of adjustments in biomass concentration (VSS) in response changes in the fed COD levels.
Figure 1. Performance of reactors A and B, respectively, for the range of specific organic loading values tested. If the sewage is more concentrated, the amount of biomass must be adjusted to maintain the same efficiency. The solids retention time (SRT) was calculated and, through the correlation between the overall consumption of COD and 1/SRT, values were estimated for the parameters biomass yield (YVSS / COD) and biomass decay rate (b). Results of this study indicate the feasibility of the activated sludge process for the treatment of the raw sugar refinery effluent, in the presence of phosphogypsum waste as a phosphorus supplement. Given the variability of the characteristics of the sewage to be treated, it was concluded that an effective and regular monitoring of some parameters, such as specific organic load and sludge age, is needed to ensure the efficiency of the plant.
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P62
GAMMA IRRADIATED CHITOSAN/pHEMA FILMS TO BE USED AS SUPPORT IN DRUG RELEASE SYSTEMS
M. H. Casimiro,a,b,* J. P. Lealc,d
[a] Unidade de Física e Aceleradores, Instituto Tecnológico e Nuclear, 2686-953 Sacavém, Portugal,
[email protected] [b] Departamento de Química, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa,
2829-516 Caparica, Portugal, [email protected] [c] Unidade de Ciências Químicas e Radiofarmacêuticas, Instituto Tecnológico e Nuclear, 2686-953
Sacavém, Portugal, [email protected] [d] Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, 1749-016
Lisboa, Portugal, [email protected] The goal of the work here presented is to obtain, by gamma radiation-induced polymerization, biocompatible and microbiological safe chitosan/poly(hydroxyethyl methacrylate) films suitable to be used as support in transdermal drug release systems.
The antimicrobial activity of obtained copolymeric films against several references strains was evaluated after inoculation. And, in order to predict which radiation dose could guarantee films microbiological safety, sub-lethal gamma radiation doses were also applied in artificially contaminated films and the Dvalues of microorganisms determined. Antibiotic release experiments were performed before and after irradiation, over amoxicillin loaded films (with different chitosan and pHEMA contents) in physiological saline solution, and vitro haemolysis tests were also performed using drug loaded membranes irradiated at different doses.
Results point out that prepared films exhibit antimicrobial properties and consequently low radiation doses are required to assure its microbiological safety. In addition results also show that, over the studied range values, drug loaded irradiated films present a fast rate of amoxicillin release and display a non-significant level of haemolysis, which suggests that the obtained films possess the capabilities to be used as transdermal carriers. Moreover, the present study also evidences one of the advantages of radiation technique by allow combining the synthesis/modification and microbiological safety in a single experiment step.
147
P63
SURFACTANT-FREE AB INITIO EMULSION POLYMERIZATION OF VINYL ACETATE USING A DEXTRAN-BASED XANTHATE AGENT SYNTHESIZED BY
CLICK CHEMISTRY
Julien Bernard,a,* Maud Save,b,c Benoit Arathoon,b Bernadette Charleuxb
(a) Ingénierie des Matériaux Polymères / Laboratoire des Matériaux Macromoléculaires (IMP / LMM),
Université - INSA Lyon, CNRS-UMR 5223, Villeurbanne, 69621, France
(b) Laboratoire de Chimie des Polymères, UMR 7610, Université Pierre et Marie Curie - CNRS, 4 place Jussieu, 75252 PARIS Cedex 05, France
(c) IPREM Equipe Physique et Chimie des Polymères, UMR 5254, Université de Pau et des Pays de l’Adour - CNRS, Technopole Hélioparc, 2 Av Président Angot, 64053 PAU cedex 9, France
Stable poly(vinyl acetate) (PVAc) submicronic latex particles are synthesized by ab initio batch emulsion polymerization using a dextran derivative as an efficient steric stabilizer1. The dextran end-functionalized by a xanthate moiety is synthesized by Huisgen’s 1,3-dipolar cycloaddition (“click chemistry”) of a chain-end propargyl-functionalized dextran (Dext-Pg) and a xanthate bearing an azido group. It is then applied as a macromolecular RAFT (Reversible Addition Fragmentation chain Transfer) agent in surfactant-free emulsion polymerization of VAc to form in-situ an amphiphilic block copolymer able to efficiently stabilize the latex particles. The method affords the preparation of high solids content (27 %) latexes with stable monodisperse PVAc nanoparticles (average DP < 200 nm) coated by a polysaccharide shell. Only a low amount (2 – 6 wt % of Dext-CTA vs. VAc) of the efficient stabilizer precursor coming from biomass is required. In comparison, the latex stabilized by either native dextran or even propargyl functionalized dextran (Dext-Pg) exhibits poor colloidal characteristics (Figure 1).
Dextran-xanthate
OH2C
O
n
S C
S
OEt
OH
OH OH
OH
Stable monodisperse PVAc nanoparticles
Native Dextran ⇒⇒⇒⇒
OH2C
O
n
OH
OH OH
OH
PolydispersePVAc
particles
⇒⇒⇒⇒
Figure 1: Route to dextran coated PVAc nanoparticles
The clear improvement of the latex properties observed when only 31 % of the dextran chains are functionalized by a xanthate moiety shows the real interest of the proposed strategy to elaborate well-defined dextran-decorated PVAc nanoparticles. Both the kinetic study and the molar mass analyses confirmed the involvement of the dithiocarbonate group in the emulsion polymerization process.
1 Bernard, J., Save, M., Arathoon, B., Charleux, B. J. Polym. Sci. Part A 2008, 46, 2845-2857.
148
AAUUTTHHOORR IINNDDEEXX
A
Abad-Romero, Beatriz OC5 Andraud, C. P51
Abdel Kader, Ouaiss P52 André, Isabelle OC13
Abrantes, Carla OC8 André, Patrice P31
Afonso, Carlos A.M. P46 Arathoon, Benoit P63
Afonso, Maria Diná OC7 Araújo, Ana C. P8
Ágoston, Károly IL28 Araújo, M. E.M. P3
Airoldi, Cristina P8 Archambault, J.-C. P31
Alfaia, António J. OC12 Arroja, Luís P60
Ali Rachedi, Fahima P50 Assalit, Aurélie P25
Amaral, M.E. P59
Amorim, Henrique IL4
B
Bajza, István IL28 Best, D. P9
Barbat, Aline P41 Bettencourt, A. P. P21, P22
Barbosa, Marta P60 Billard, Thierry P25
Barrault, Joël OC1, P23 Blériot, Yves P6
Barreto, V. P57 Blum, L. P51
Barsu, C. P51 Bonnet, V. OC3
Beirão-da-Costa, Maria L.
P47 Booth, K. V. OC15
Beláňová, M. P15 Bordado, João P19, P24,P61
Belgsir, E.M. P26 Borges, Carlos P20
Benito, E. P54 Bosco, M. P32, P33
Bento, Luis San Miguel IL5 Boullanger, Paul P39
Benvegnu, Thierry IL17 Boutet, Julien OC13
Bercier, Ariane IL12 Branco, Luís C. P46
Bernal-Albert, Paloma P12 Bretonnière, Y. P51
Bernard, Julien P52, P63 Bruggink, Cees IL 24, P57
149
C
Cabral, J.M.S. OC2 Champion, Elise OC13
Calado, António T. OC12 Charleux, Bernadette P63
Campoy, Rocio P3 Cheaib, R. P14
Capela, Isabel P60 Chiacchio, Maria A. P22
Cardoso, Susana M. IL15 Christensen, Bjørn E. OC6
Carvalheiro, Florbela OC9 Cipollab, Laura P8
Carvalho, Ana P. P17 Cocchi, L. P32
Carvalho, Filipe OC2 Coe, Diane P25
Carvalho, João F. S. P16 Coimbra, Manuel A. IL15
Casimiro, Maria Helena IL 13, P62 Correia, Paula M. P47
Castanheiro, J.E. P42 Corsaro, Antonino P22
Catelanib, Giorgio P22 Costa, Barbara P8
Cattorini, Stefano OC2 Covis, Rudy P27
Cecioni, Samy OC14 Cowling, Stephen J. P50
Cenatiempo, Y. P26 Cuny, Eckehard OC10, P7
Champion, Elise OC13 Chambert, Stéphane P14, P25, P34, P50, P52 Charleux, Bernadette P63
D
De Braeckelaer, P. P45 Diogo, Hermínio P. P58
de Pinho, Maria N. OC7 Djedaïni-Pilard, F. OC3, P26, P31
Deelder, A. M. P57 Domingues, F.C. P59
Defaye, Jacques IL10 Doutheau, Alain P34
Dékány, Gyula IL28 Duarte, Ana P. OC8, P59
Delample, Mathieu P23 Duarte, Luís C. OC9
Descroix, Karine OC13 Duarte, M.T. P61
Di Renzo, Francesco P48 Ducatel, Hélène P45
Dias, Ana S. P44 Durães, C. P18
Dias, Andreia P55 Durand, Alain P27
Dias, T.A. P18 Durand, Morgan OC11, P35
E
Escudero, Rosalia R. P48 Esteves, A.P. P18
Essers, Maurice P45 Fabbian, M. P32, P33
150
F
Fenet, Bernard P34 Fleury, Etienne P52
Ferchaud, Pierre P45 Florêncio, M. Helena P5
Fernandes, Pedro OC2 Fonseca, I.M. P42
Ferreira, Dulcineia IL14 Fonseca, Tiago P24
Figueiredo, José A. OC8, P3 Fournez, Antoine P30
Fleet, G. W. J. OC15, P9 Fuertes, Patrick IL2
G
Galbis, Juan A. IL3, P38, P54 Goodby, John W. P50
Gallezot, Pierre P29 Godé, Paul P31
Gálvez, Julio IL26 Gómez, Ana M. P12
Gómez-García, M. P37 García Fernandez, J.M. Il10, IL26, P30, P37 Gouin, S.G. P36
García-Martín, M. Gracia P54 Goulart, Margarida P3, P6, P20
Gianni, R. P32, P33 Goumain, Sophie IL12
Gil, Luis P49 Granet, Robert P53
Gil, N. P59 Gruber, Clemens OC5
Girard-Ergot, A. P51 Guérin, David IL31
Gírio, Francisco M. OC9, P55, P56 Guilbot, Jérôme P34
Girón-González, M. D. P37 Guisnet, Michel P17
Gloaguen, Vincent P41 Gullón, Patrícia P56
H
Hamaide, Thierry P39 Herok, Wilhelm OC5
Hamon, F. P26 Higham, R. P9
Helleputte, Murielle P28 Hokke, C. H. P57
Hendrickx, Johann IL17
I
Imberty, Anne OC14 Ismael, M. Isabel OC8, P3
Ingendoh, A. P57
J
Jacob, Ana P. P6 Jérôme, François OC1, P23
Jarosz, Slawomir IL7 Jesus, Ana R. P17
Jenkinson, S. F. P9 Justino, Jorge P2, P3, P6, P20
Jensen, Detlef IL24
151
K
Kachkarova, Svetlana L. P29 Kosma, Paul OC5
Karam, Ayman OC1, P23 Kovensky, José P36, P40
Karche, Navnath P11 Krausz, Pierre P41, P53
Kerverdo, Sébastien P34 Křen, Vladimír IL21
Kitamura, Shinichi IL9 Kristiansen, Kåre A. OC6
Koeleman, C. A. M. P57 Kröger, Lars IL28
L
Ladavière, Catherine P27 Lesur, David P30, P31
Lafont, Dominique P39 Lichtenthaler, F. W. IL32, OC10, P7
Lambin, Anne OC4 Lima, Sérgio P43, P44
Langlois, Bernard P25 Listkowski, A. P14
Laurent, Pascal P28 Lopes-da-Silva, J.A. IL15
Le Deit, Hervé IL17 López, J. Cristóbal P12
Leal, João P. IL13, P62 Lucas, Susana D. P10
Leclerc, Eric P11 Lui, Y. P57
Len, C. P26 Lundt, Inge IL28
Lerat, Yannick IL17
M
Madeira, Paulo J. A. P5 Mesnager, Julien OC4
Marcelo, Filipa P6 Michaud, Philippe P40
Marhol, Petr IL21 Mikušová, K. P15
Marie, Emmanuelle P27 Moebs, Sylvie P52
Marques, Marco. P.C. OC2 Molinier, Valérie OC11, P35
Marques, Susana P55 Monsan, Pierre OC13
Marra, Alberto IL19 Moreau, Vincent P31
Martins, Suzana OC8 Morel, Sandrine OC13
Matthews, Susan E. OC14 Moreno, Benjamin P11
Maury, O. P51 Moser, Matthias IL6
Medeiros, M.J. P18 Mota-Filipe, Hélder P20
Meireles, Margarida P4 Moulis, Claire OC13
Méndez-Ardoy, Alejandro
P37 Moura, Patrícia P55, P56
Mercer, T. B. P9 Mulard, Laurence A. OC13
152
N
Nadais, Helena P60 Nogueira, José P19
Neng, Nuno P19 Noronha, João P. P20
Newell, R. J. P9 Nott, Katherine P28
Nicotra, Francesco P8 Nunes, S. M. P61
O
Ortiz Mellet, Carmen IL10, IL26, P30, P37
Otman, Otman P39
Oscarson, Stefan IL22
P
Paquot, Michel P28 Pinheiro, H. M. P61
Parajó, Juan Carlos P56 Pinheiro, J. M. P3
Parpot, Pier P21, P22 Pinto, B. Mario IL20
Paz, M. Violante de P38 Pinto, Rui P20
Penadés, Soledad IL8 Pinto, Susana S. P58
Pereira, Carlos P49 Pistarà, Venerando P22
Pérez, Serge IL1 Pito, D.S. P42
Perly, B. OC3 Plantier-Royon, R. IL12
Petruš, L. P15 Plusquellec, Daniel IL17
Petursson, S. P9 Pohl, C. P57
Philippe, Michel IL16 Poláková, M. P15
Picotti, F. P32, P33 Portella, Charles IL12
Pierre, Ronan OC1 Postel, Denis P45
Pilard, Serge P30 Poulain, Florent P11
Pillinger, Martyn P43, P44 Praly, Jean-Pierre OC14
Pinel, Catherine OC4 Prates, António OC7, P60
Q
Quignard, Françoise IL30, P48 Queneau, Y. OC1, P15, P25, P34, P50, P51, P52
Quirion, Jean-C. P11
Quettier, Claude OC4
153
R
Ramôa Ribeiro, F. P17 Ringot, Cyril P53
Ramos, A.M. P42 Riva, Sergio P16
Ramos, Joaquim J. M. P58 Robitzer, Mike P48
Raposeiro, Inês P24 Rolland, Hervé P34
Rastall, Robert IL25 Rollin, Patrick P1, P2
Rat, Stéphanie P40 Rosa, Ana M. T. G. P5
Richel, Aurore P28 Rosatella, Andreia A. P46 Roseiro, Luísa P20
Rauter, Amélia P. OC16, P1, P2, P3, P4, P5, P6, P8, P10, P13, P14, P17, P19 Roussel, Myriam IL17
Remaud-Siméon, Magali OC13 Roux, M. OC3
Restolho, José A. OC7 Rubio, Luis A. IL26
Ribeiro, Maria H.L. OC12 Ruiz, Raquel IL26
Richard, Gaëtan P28 Rule, S. D. P9
S
Sá e Melo, M. Luísa P16 Silva-Fernandes, T. OC9
Salto-González, Rafael P37 Simão, Ana C. P1
Samain, Daniel IL31 Simões, Rogério OC8
Santos, Miguel M. P17 Simões, Sérgio P16
Santos, Rui G. P19 Sinaÿ, Pierre P6, P13
Santoyo-González, F. P37 Sixta, Georg OC5
Sardinha, João P13 Sixta, Herbert OC5
Sassi, Jean-François IL17 Sol, Vincent P53
Save, Maud P63 Sollogoub, Matthieu P13
Sepúlveda, Catarina P4 Sorokin, A. B. P29
Sevillano-Tripero, N. P37 Stinga, Camélia IL31
Silva, Artur M. S. P3 Striegel, André M. IL29
Silva, Filipa V. M. P2, P3, P6 Stucchi, L. P32, P33
Silva, Flávio P60 Stütz, Arnold IL28
Silva, M. Manuel C. P16 Suárez-Pereira, E. P30
Silva, Sandrina P2
T
Tatibouët, Arnaud P1, P2 Trevisan, A. P32, P33
Thiebault, Nicolas P31 Turpin, F. P26
Thiem, Joachim IL28
154
U
Uriel, Clara P12
V
Valente, Anabela A. P43, P44 Villandier, Nicolas OC1, P23
Ventura, Juan P12 Violeau, B. P26
Vicente, V. M. P61 Viot, Camille P45
Vidal, Sébastien OC14 Vital, J. P42
Vierling, Pierre IL10 Vliegenthart, J. F.G. IL27
Vila-Real, Helder OC12 Vogel, Pierre IL11
W
Wadouachi, Anne P40 Wessel, Hans Peter IL18, P10
Wagner, Anne P45 Weymouth-Wilson, A.C. P9
Wathelet, Jean-Paul P28 Woods, Robert J. IL23
Weignerová, Lenka IL21 Wuhrer, M. P57
X
Xavier, Nuno M. OC16, P4, P5, P14
Z
Zamora, Francisca P38 Zhu, Ying OC11, P35
Zarzuelo, Antonio IL26 Zoboli, Rossella P8
155
LLIISSTT OOFF PPAARRTTIICCIIPPAANNTTSS
A Abdel Kader, Ouaiss INSA Lyon Laboratoire de Chimie Organique Bâtiment J. Verne, Villeurbanne France [email protected] Ágoston, Károly Glycom A/S; Building 201 Danish Technical University Lyngby, 2800 Kgs Denmark [email protected] Ali Rachedi, Fahima INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne, France Amorim, Henrique Fermentec Ltda Av. Antonia Pizzinato Sturion 1155 Jd. Petrópolis, CP 13420640, Cep: 13420640 Piracicaba SP Brasil [email protected] Andre, Isabelle Université de Toulouse; INSA,UPS,INP, LISBP 135 Avenue de Rangueil, F-31077 Toulouse France [email protected]
Araújo, Ana Catarina Carbohydrate Chemistry Group Centro de Química e Bioquímica Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Edifício C8, 5º Piso, Campo Grande, 1749-016, Lisboa, Portugal [email protected] Araújo, Maria Eduarda Carbohydrate Chemistry Group Centro de Química e Bioquímica Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Edifício C8, 5º Piso, Campo Grande, 1749-016, Lisboa, Portugal [email protected] Assalit, Aurélie Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, Laboratoire SERCOF, 43 Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France [email protected]
B
Bento, Luís San Miguel Sucropedia [email protected] Benvegnu, Thierry Ecole Nationale Supérieure de Chimie de Rennes UMR CNRS 6226 "Sciences Chimiques de Rennes", Equipe "Chimie Organique et Supramoléculaire" Av. G. Leclerc 35700 Rennes France [email protected]
Bernard, Julien Ingénierie des Matériaux Polymères / Laboratoire des Matériaux Macromoléculaires (IMP / LMM), Université - INSA Lyon CNRS-UMR 5223, Villeurbanne, 69621 France [email protected]
Besset, Céline INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne, France [email protected]
156
Best, Daniel Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK [email protected] Booth, Kathrine Victoria Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK [email protected] Bordado, João IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa Portugal [email protected]
Borges, Carlos Centro de Química e Bioquímica Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa Ed. C8, Campo Grande, 1749-016 Lisboa, Portugal [email protected] Bosco, Marco Sigea Srl S.r.l.,Area Science Park, Padriciano 99, 34012 Trieste, Italy [email protected] Bruggink, Cees Dionex Benelux BV Abberdaan 114, 1046 AA Amsterdam Netherlands [email protected]
C Campoy, Rocio Centro de Química e Bioquímica Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Edifício C8, 5º Piso, Campo Grande, 1749-016,Lisboa, Portugal [email protected] Carvalheiro, Florbela INETI, Departamento de Biotecnologia, Estrada do Paço do Lumiar 22, P-1649-038 Lisboa, Portugal [email protected] Carvalho, Ana Paula Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Edifício C8, 5º Piso, Campo Grande, 1749-016,Lisboa, Portugal [email protected] Carvalho, João Fernando dos Santos Centro de Estudos Farmacêuticos, Lab. Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Rua do Norte 3000-295, Coimbra, Portugal [email protected]
Cecioni, Samy ICBMS/Laboratoire de Chimie Organique 2–Glycochimie/UMR 5246, Université Claude Bernard Lyon 1, CNRS, 43 Blvd du 11 Novembre 1918, F-69622 Villeurbanne, France [email protected] Chambert, Stéphane INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne, France [email protected] Christensen, Bjørn E. NOBIPOL, Department of Biotechnology, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim Norway [email protected] Coimbra, Manuel A. Departamento de Química Universidade de Aveiro 3810-193 Aveiro, Portugal [email protected]
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Correia, Paula Departamento de Indústrias Alimentares, Escola Superior Agrária do Instituto Politécnico de Viseu. Quinta da Alagoa Estrada de Nelas, 3500-606 Viseu Portugal [email protected] Costa, Júlia ITQB-UNL Apartado 127, 2780-901 Oeiras Portugal [email protected]
Covis, Rudy Laboratoire de Chimie Physique Macromoléculaire, UMR 7568 CNRS - Nancy-University, ENSIC, 1 rue Grandville, BP 20451, F-54001 Nancy cedex, France [email protected] Cuny, Eckehard Institut für Organische Chemie, Technische Universität Darmstadt, D-64287 Darmstadt Germany [email protected]
D Defaye, Jacques Dept. de Pharmacochimie Moleculaire, Institut de Chimie Moleculaire de Grenoble CNRS – Univ. Grenoble, UMR 5063, FR2607, F-38041 Grenoble, France [email protected] Delample, Mathieu Laboratoire de Catalyse en Chimie Organique, Université de Poitiers/CNRS 40 Avenue du recteur Pineau, 86022 Poitiers, France [email protected] Deliencourt-Godefroy, Géraldine TFChem France [email protected] Descotes, Gerard University Lyon I Bat. 308-CPE 43 Bd du 11 Novembre 1918 69622 Villeurbanne Cedex France [email protected]
Di Renzo, Francesco Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-ENSCM-UM1, Matériaux Avancés pour la Catalyse et la Santé, ENSCM, 8 rue Ecole Normale, 34296 Montpellier Cedex 5, France [email protected] Djedaini-Pilard, Florence UMR6219, Université de Picardie-Jules Verne 33 rue Saint-Leu, F-80039 Amiens France [email protected]
Duarte, Luís C. INETI, Departamento de Biotecnologia, Estrada do Paço do Lumiar 22, P-1649-038 Lisboa, Portugal [email protected] Durand, Morgan LCOM - UMR CNRS 8009 - Oxydation et Physico-Chimie de la Formulation, Ecole Nationale Supérieure de Chimie de Lille F-59652 Villeneuve d'Ascq France
E Epoune, Cedric ITERG Spain [email protected]
Esteves, Ana Paula Centro de Química, Universidade do Minho, Largo do Paço, 4704-553 Braga, Portugal [email protected]
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Estevez, Ramon J. Departamento de Química Orgánica University of Santiago de Compostela 15782 Santiago de Compostela Spain [email protected]
F Ferchaud, Pierre Centre de Valorisation des Glucides, 33 avenue Paul Claudel, 80480 Dury France [email protected] Fernandes, Pedro Institute for Biotechnology and Bioengineering/Centre for Biological and Chemical Engineering/ Instituto Superior Técnico Av. Rovisco Pais, P-1049-001 Lisboa Portugal [email protected] Ferreira, Dulcineia Agricultural Polytechnic School of Viseu, 3500-606 Viseu Portugal [email protected]
Joana, Ferreira Centro de Química e Bioquímica/Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa Ed. C8, 5º piso, 1749-016 Lisboa Portugal Figueiredo, Albertino Research Unit of Textile and Paper Materials, University of Beira Interior, P-6201-001 Covilhã Portugal [email protected] Fuertes, Patrick Roquette Frères F-62080 Lestrem CEDEX France [email protected]
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Galbis, Juan Department of Organic and Pharmaceutical Chemistry, University of Seville C/Prof. García González, 2; 41012-Seville Spain [email protected] García Fernandez, Jose M. Instituto de Investigaciones Químicas, CSIC - Univ. Sevilla, E-41092 Sevilla, Spain [email protected] Garcia-Martin, M. Gracia CSIC - Univ. Sevilla, E-41092 Sevilla, Spain [email protected] Gaspar, Natália Instituto Politécnico de Santarém Portugal [email protected]
Gloaguen, Vincent Université de Limoges, Laboratoire de Chimie des Substances Naturelles, UPRES EA 1069-GDR CNRS 3049, 123 rue Albert Thomas, LIMOGES 87060, France [email protected] Godinho, Joana Instituto Politécnico de Santarém Portugal [email protected] Gouin, Sébastien Laboratoire des Glucides, UMR 6219, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens, France [email protected]
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H Herold, Bernardo Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa Portugal [email protected] Holst, Otto Lübeck University Ratzeburger Allee 160, Lübeck Germany [email protected]
Humanes, Madalena Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa Ed. C8, 5º piso, 1749-016 Lisboa Portugal
I Ismael, Isabel Research Unit of Textile and Paper Materials, University of Beira Interior, P-6201-001 Covilhã Portugal [email protected]
J Jaakkola, Virpi Hannele Technical Research Centre of Finland Finland [email protected] Jarosz, Slawomir Institute of Organic Chemistry, Polish Academy of Sciences Kasprzaka 44/52, 01-224 Warsaw Poland [email protected] Jerome, Francois Laboratoire de Catalyse en Chimie Organique, CNRS-Université de Poitiers, 40 avenue du recteur Pineau, F-86022 Poitiers, France [email protected]
Jesus, Ana Rita Carbohydrate Chemistry Group Centro de Química e Bioquímica Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Edifício C8, 5º Piso, Campo Grande, 1749-016, Lisboa, Portugal [email protected] Jorge, Estrela Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Edifício C8, 5º Piso, Campo Grande, 1749-016, Lisboa, Portugal Justino, Jorge Escola Superior Agrária de Santarém Quinta do Galinheiro, Apartado 310, 2001-904 Santarém, Portugal [email protected]
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K Kerverdo, Sébastien SEPPIC, 127 chemin de la Poudrerie, BP 228, 81105 Castres cedex France [email protected] Kitamura, Shinichi Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531 Japan [email protected] Kosma, Paul University of Natural Resources and Applied Life Sciences, Department of Chemistry, Muthgasse 18, A-1190 Vienna Austria [email protected]
Krausz, Pierre Université de Limoges, Laboratoire de Chimie des Substances Naturelles, UPRES EA 1069-GDR CNRS 3049, 123 rue Albert Thomas, Linoges 87060, France [email protected] Kren, Vladimir Institute of Microbiology, Academy of Sciences of the Czech Republic Laboratory of Biotransformation National Centre of Biocatalysis and Biotransformation Videnska 1083 CZ 142 20 Praha 4, Czech Republic [email protected] Kristiansen, Kåre A. NOBIPOL, Department of Biotechnology, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway [email protected]
L Leal, João Paulo Unidade de Ciência Químicas e Radiofarmaceuticas, ITN 2686-953 Sacavém Portugal [email protected] Leclerc, Eric IRCOF, COBRA, UMR 6014 CNRS, Université et INSA de Rouen, 1 rue Lucien Tesnière 76130 Mont Saint-Aignan, France [email protected] Len, Christophe Synthèse et Réactivité des Substances Naturelles, UMR6514 Université de Poitiers-CNRS, 40 avenue du Recteur Pineau, 86022 Poitiers, France [email protected]
Lichtenthaler, Frieder Clemens-Schöpf-Institut für Organische Chemie und Biochemie Technische Universität Darmstadt Petersenstraße 22, Darmstadt, D-64287 Germany [email protected] Lima, Sérgio CICECO, University of Aveiro Portugal [email protected] López, Cristóbal Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain [email protected]
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Luazi Matos de Oliveira, Diana The University of Reading, PO Box 226, Whiteknights, Reading, RG6 6AP United Kingdom [email protected]
Lucas, Susana Dias Carbohydrate Chemistry Group Centro de Química e Bioquímica Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Edifício C8, 5º Piso, Campo Grande, 1749-016, Lisboa, Portugal [email protected]
M Madeira, Paulo Centro de Química e Bioquímica/ Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, Campo Grande, 1749-016 Lisboa Portugal [email protected] Marques, Susana INETI - DB Estrada do Paço do Lumiar 22, P-1649-038 Lisboa, Portugal [email protected] Marra, Alberto Dipartimento di Chimica, Università di Ferrara Via Borsari 46, 44100 Ferrara Italy [email protected] Martins, Alice Carbohydrate Chemistry Group Centro de Química e Bioquímica/ Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016 Lisboa, Portugal [email protected] Maycock, Christopher Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016 Lisboa, Portugal [email protected]
Medeiros, Margarida Goulart de Instituto Tecnológico e Nuclear, Unidade de Protecção e Segurança Radiológica, E.N.10, Apartado 21, 2686-953 Sacavém Portugal [email protected] Meireles, Margarida Centro de Química e Bioquímica/ Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016 Lisboa, Portugal [email protected] Méndez-Ardoy, Alejandro. Departamento de Química Orgánica, Facultad de Química, Univ. Sevilla, Sevilla E-41012, Spain [email protected] Moebs, Sylvie INSA Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, Villeurbanne France [email protected] Molinier, Valérie LCOM - UMR CNRS 8009 - Oxydation et Physico-Chimie de la Formulation, F-59652 Villeneuve d'Ascq France [email protected] Moreau, Vincent Laboratoire des Glucides, CNRS-UMR 6219, Institut de Chimie de Picardie, Université de Picardie Jules Verne, 33 rue St Leu, 80039 Amiens, France [email protected]
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Morin, Christophe DCM - Université Grenoble LEDSS Chimie Recherche Batiment 52 Campus de l’Uif 38402 St. Martin d’Hèrés France [email protected] Moser, Matthias Südzucker AG Mannheim/Ochsenfurt, Central Department Research, Development, and Technological Services (CRDS) Wormser Str. 11 Germany [email protected]
Moura, Patrícia INETI – DB Estrada do Paço do Lumiar 22, P-1649-038 Lisboa, Portugal [email protected] Mulard, Laurence Unité de Chimie des Biomolécules, URA CNRS 2128, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris cedex 15, France [email protected]
N Nicotra, Francesco Università degli Studi di Milano-Bicocca Dipartimento di Biotecnologie e Bioscienze Piazza della Scienza 2, I-20126 Milano, Italy Italy [email protected]
Noéme, Carlos ISA-UTL Portugal
O Ortiz Mellet, Carmen Dpto. de Química Orgánica, Facultad de Química, Univ. Sevilla, E-41012 Sevilla, Spain [email protected] Oscarson, Stefan University College Dublin Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology Ireland [email protected]
Otman, Otman Université Lyon 1 ; Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Chimie Organique 2 – Glycochimie, CNRS UMR 5246, CPE-Lyon. 43, boulevard du 11 Novembre 1918, Villeurbanne, F-69622, France [email protected]
P Paiva, Ana Paula Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, Campo Grande, 1749-016 Lisboa Portugal [email protected]
Paulsen, Berit School of Pharmacy, University of Oslo P.O.Box 1068 Blinoeriv 0316 Oslo Norway [email protected]
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Paz Báñez, M. Violante de Departamento de Química Orgánica y Farmacéutica. Universidad de Sevilla. C/ Profesor García González nº 2, 41012 Sevilla, Spain [email protected]
Penades, Soledad Laboratory of GlycoNanotechnology, CICbiomaGUNE and Networking Centre on Bioengineering, Biomaterials, and Nanomedicine, CIBER-BBN Parque Tecnológico de San Sebastian, Paseo de Miramon 182, 20009 San Sebastian Spain [email protected] Perez, Serge Centre de Recherches sur les Macromolécules Végétales, Centre National de la Recherche Scientifique B.P. 53X, 38041 Grenoble Cédex 09 France [email protected] Philippe, Michel L'Oréal R&D Green Chemistry Manager Cell. : 33 6 61 24 23 03 1, avenue Eugène Schueller, 93600 Aulnay sous bois France [email protected] Picotti, Fabrizio Sigea Srl S.r.l.,Area Science Park, Padriciano 99, 34012 Trieste, Italy [email protected]
Pinel,Catherine Université de Lyon ; Institut de Recherches sur la Catalyse et l’Environnement de Lyon 2 avenue Albert Einstein F-69626 Villeurbanne France [email protected] Pinto, B. Mario Simon Fraser University Room 3195 Strand Hall, 8888 University Drive, Burnaby, B.C. Canada V5A 1S6 Canada [email protected] Pinto, Susana Centro de Química-Física Molecular and IN-Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade Técnica de Lisboa, 1049-001 Lisboa, Portugal [email protected] Pito, Dália Centro de Química de Évora, Departamento de Química, Universidade de Évora, 7000-671 Évora, Portugal [email protected] Poláková, Monika Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 38 Bratislava, Slovakia [email protected] Portella, Charles Faculty of Sciences, Université de Reims Champagne-Ardenne Institut de Chimie Moléculaire de Reims, CNRS UMR 6229, UFR Sciences Exactes et Naturelles, BP 1039, 51687 Reims Cedex 2, France [email protected]
Q Queneau, Yves Laboratoire de Chimie Organique, INSA Lyon, Bât. Jules Verne 20 avenue Albert Einstein, 69621 Villeurbanne Cedex, France [email protected]
Quignard, Françoise Institut Charles Gerhardt Montpellier- UMR 5253- CNRS-UMII-ENSCM-UMI Matériaux Avancés pour la Catalyse et la Santé 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France [email protected]
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R Ramôa Ribeiro, Fernando Centro de Engenharia Biológica e Química, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa Portugal [email protected]. Rastall, Robert Department of Food Biosciences, The University of Reading, PO Box 226, Whiteknights, Reading, RG6 6AP United Kingdom [email protected] Rauter, Amélia Pilar Carbohydrate Chemistry Group Centro de Química e Bioquímica/ Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, Ed. C8, 5º piso, 1749-016 Lisboa Portugal [email protected] Restolho, José Technical University of Lisbon, Instituto Superior Técnico, Department of Chemical and Biological Engineering, Av. Rovisco Pais, 1, P-1049-001 Lisboa Portugal [email protected]
Richard, Gaëtan Unit of Biological Chemistry, Gembloux Agricultural University, Passage des Déportés, 2, B – 5030 Gembloux, Belgium [email protected] Ringot, Cyril Université de Limoges, Laboratoire de Chimie des Substances Naturelles, UPRES EA 1069-GDR CNRS 3049, 123 avenue Albert Thomas, 87060 Limoges, France [email protected] Rollin, Patrick 1 ICOA – UMR 6005, Université d‘Orléans BP 6759, F-45067 Orléans France [email protected] Rosatella, Andreia de Almeida IST/UTL Av. Rovisco Pais, 1, P-1049-001 Lisboa Portugal [email protected] Roseiro, Luisa Bivar Departamento de Biotecnologia, INETI - Instituto Nacional de Engenharia, Tecnologia e Inovação, IP Estrada do Paço do Lumiar, 22, 1649-038 Lisboa Portugal [email protected]
S Samain, Daniel CERMAV-CNRS BP 53 38041 Grenoble cedex 9 France [email protected] Santos, Fernando Centro de Química e Bioquímica/ Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, Ed. C8, 5º piso, 1749-016 Lisboa, Portugal [email protected]
Santos, Helena ITQB/UNL Apartado 127, 2780-901 Oeiras Portugal [email protected] Santos, Maria Soledade Centro de Química e Bioquímica/ Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa,Edifício C8, Campo Grande, 1749-016,Lisboa, Portugal [email protected]
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Santos, Rui Galhano dos Carbohydrate Chemistry Group Centro de Química e Bioquímica/ Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Ed. C8, 5º piso, 1749-016 Lisboa, Portugal [email protected] Santos, Susana Centro de Química e Bioquímica/ Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Ed. C8, 5º piso, 1749-016 Lisboa, Portugal [email protected] Santoyo, Francisco Dpto. de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología, Univ. de Granada, E-18071 Granada, Spain [email protected] Sardinha, João Carbohydrate Chemistry Group Centro de Química e Bioquímica/ Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Ed. C8, 5º piso, 1749-016 Lisboa, Portugal [email protected] Scherrmann, Marie-Christine ICMMO Orsay France [email protected]
Silva, Filipa V.M. Carbohydrate Chemistry Group Centro de Química e Bioquímica/ Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Ed. C8, 5º piso, 1749-016 Lisboa, Portugal Simão, Ana Catarina ICOA – UMR 6005, Université d‘Orléans, BP 6759, F-45067 Orléans, France France [email protected] Sol, Vincent Université de Limoges, EA 1069-GDR CNRS 3049, 123 rue Albert Thomas, Linoges 87060, France [email protected] Spúlveda, Catarina Carbohydrate Chemistry Group Centro de Química e Bioquímica/ Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de Lisboa, Ed. C8, 5º piso, 1749-016 Lisboa, Portugal [email protected] Striegel, Andre Department of Chemistry & Biochemistry, Florida State University Tallahassee, FL 32306-4390 USA [email protected] Suárez Pereira, Elena Dpto. de Química Orgánica, Facultad de Química, Univ. Sevilla, Sevilla E-41012, Spain [email protected]
T Talja, Helina Technical Research Centre of Finland Finland [email protected]
Thiem, Joachim University of Hamburg Germany [email protected]
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U Uriel, Clara Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain [email protected]
V Valente, Anabela Aguiar CICECO, University of Aveiro 3810-193 Aveiro, Portugal [email protected] Vila-Real, Helder Institute for Medicines and Pharmaceutical Sciences (i-Med), Faculdade de Farmácia, University of Lisbon, Av. Prof. Gama Pinto, P-1649-003 Lisbon, Portugal [email protected]; [email protected]
Vliegenthart, Johannes Bijvoet Center, Utrecht University, Utrecht, The Netherlands [email protected] Vogel, Pierre Laboratory of glycochemistry and asymmetric synthesis (LGSA), Swiss Federal Institute of Technology in Lausanne (EPFL) Batochime, CH 1015 Lausanne, Switzerland [email protected]
W Wadouachi, Anne Laboratoire des Glucides UMR 6219 CNRS, Université de Picardie Jules Verne, 33 rue Saint-Leu, 80039 Amiens cedex, France [email protected] Wessel, Hans Peter F. Hoffmann-La Roche Ltd., Pharmaceutical Research, Discovery Chemistry
CH-4070 Basel, Switzerland
Woods, Robert SFI Research Professor, University of Georgia, Complex Carbohydrate Research Center,315 Riverbend Road, Athens, GA 30602 USA [email protected]
X Xavier, Nuno Manuel Carbohydrate Chemistry Group Centro de Química e Bioquímica/ Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa,Ed. C8, 5º Piso, Campo Grande, 1749-016 Lisboa Portugal [email protected]
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Z Zamora, Francisca Departamento de Química Orgánica y Farmacéutica. Universidad de Sevilla. C/ Profesor García González nº 2, 41012 Sevilla, Spain [email protected]