arvind jaganathan michigan state university january 21 st 2009
TRANSCRIPT
Arvind JaganathanMichigan State University
January 21st 2009
1
Biosynthesis and biomimetic synthesis
O2, NADPHSqualene Monooxygenase
Squalene
Biosynthesis of Steroids
2
Squalene Monooxygenase
O
2,3(S)-Epoxysqualene
Dugas, H.; Bioorganic Chemistry : A Chemical Approach to Enzyme Action, Springer – Verlag, New York, 1988, chap. 5, p. 383
Exploration of Chemical Space by Nature
O
chair-chair-chair-boat
-AmyrineSynthase
HO
H
H
HH
Transient Carbocation
Glacial AcOH
3
HO
H
H
H
-Amyrine
Glacial AcOH1 day
No reaction
Wu, T.K.; Chang, C.H.; Liu, Y.T.; Wang, T.T.; Chem.Rec., 2008, 8, 302
Exploration of Chemical Space by Nature
4
Wu, T.K.; Chang, C.H.; Liu, Y.T.; Wang, T.T.; Chem.Rec., 2008, 8, 302
Nature relies on different enzymes for making different natural products even if the
precursor to all these natural products is the same.
Challenges in mimicking nature
• It is often difficult to control side reactions.
• It is difficult to access molecules which are formed from more energetic transition states.
5Dugas, H.; Bioorganic Chemistry : A Chemical Approach to Enzyme Action, Springer – Verlag, New
York, 1988, chap. 5, p. 383
Biomimetic Synthesis
• Biomimetic Chemistry is novel chemistry inspired by that done in
living systems – Ronald Breslow
• Biomimetic synthesis aims to identify biosynthetic patterns that can • Biomimetic synthesis aims to identify biosynthetic patterns that can
be exploited in the laboratory without the sophisticated catalysis,
pre-organization and compartmentalization used in nature. – Dirk
Trauner
6
Breslow, R.; Chem.Soc.Rev., 1972, 1,553Volgraf, M.; Lumb, L.P.; Brastian, H.C.; Carr, G.; Marco, K.; Chung, W.; Munzel, M.; Mauk, A.G.;
Andersen, R.J.; Trauner, D. Nature Chem. Bio., 2008, 4, 535
Nature’s natural product assembly line : Role of enzymes
• Enzymes play a pivotal role in accelerating reaction rates and pre-organizing molecules in appropriate orientations before bond formation.
• Bond formation may be very facile even in what may be perceived • Bond formation may be very facile even in what may be perceived as energetically unfavorable conformations.
• In almost all cases, the structural complexity of natural products is attributable to enzymes.
• But synthesis of enzymes has biogenetic roots and is quite energy consuming.
7
Are enzymes the solitary source of natural products’ complexity and diversity?
Photoisomerization of 7-Dehydrocholesterol to Vitamin D3
8Dugas, H.; Bioorganic Chemistry : A Chemical Approach to Enzyme Action, Springer – Verlag, New
York, 1988, chap. 5, p. 383
Photoisomerization of 7-Dehydrocholesterol to Vitamin D3
Dugas, H.; Bioorganic Chemistry : A Chemical Approach to Enzyme Action, Springer–Verlag, New York, 1988, chap. 5, p. 383
What is non-enzymatic self-assembly important for any organism?
• It is an additional pathway available for exploration of chemical
space by nature.
• Biosynthesis of an enzyme is a highly energy consuming process;
hence avoiding the use of enzymes will be a very economical way of
accessing natural products.
Enzyme biosynthesis
Crick, F.; Nature, 1970, 227, 561http://en.wikipedia.org/wiki/Central_dogma
Unique structural features of some natural products –Pointers to a non-enzymatic mechanism?
H
H
Ph
HH
H
CO2HH
Endiandric Acid A
8 contiguous stereocentersExists as a racemate in nature
12
Occurrence of motifs easily obtained without enzyme assistance
13
Occurrence of Motifs easily obtained without enzyme assistance
How does one prove that spontaneous assembly of natural products is possible?
• If one is to invoke a non-enzymatic mechanism for the formation ofnatural products, it must be possible to make them usingconventional chemical synthesis.
• If synthetic mimics of reactive biosynthetic precursors can be made,they should spontaneously react without enzyme mediation to givethey should spontaneously react without enzyme mediation to givenatural products.
• Biomimetic synthesis aims to identify biosynthetic patterns that canbe exploited in the laboratory without the sophisticated catalysis,pre-organization and compartmentalization used in nature. – DirkTrauner
15Volgraf, M.; Lumb, L.P.; Brastian, H.C.; Carr, G.; Marco, K.; Chung, W.; Munzel, M.; Mauk, A.G.;
Andersen, R.J.; Trauner, D. Nature Chem. Bio., 2008, 4, 535
Few of the possible biosynthetic routes of spontaneous assembly
1. Electrocyclizations.
2. Dimerization.2. Dimerization.
3. Cascade Reactions
16
Electrocyclizations
• The activation barriers for 8π electrocyclization reactions are
generally low (typically ~ 20kCal/mol).
• There is very little literature precedence for catalysis of any sorts in • There is very little literature precedence for catalysis of any sorts in
electrocyclization reactions.
• Asymmetric/enzyme mediated electrocyclizations are extremely
rare.
17Huisgen, R.; Dahmen, A.; Huber, H.; J.Am.Chem.Soc. 1967, 89, 7130
Bishop, L.M.; Barbarow, J.E.; Bergman, R.G.; Trauner, D. Angew. Chem. Int.Ed., 2008, 47, 8100
Thermal 6π and 8π electrocyclizations
18Woodward, R.B.; Hoffmann, R.; J. Am. Chem. Soc., 1965, 87, 395
SNF4435 C and D
• SNF4435 C and D were isolated from the culture broth of Streptomyces spectabilis in 2001.
• They are optically active polyketides that have been isolated as 3:1 mixture.
O
O
O
OMe
O2N
Me
SNF4435 C
O
OO2N
• Spectinabillin had already been isolated from S.spectabilis in 1976.
• It was proposed that Spectinabilincould be the common biosynthetic precursor for both SNF4435 C and SNF4435 D
19Kurosawa, K.; Takahashi, K.; Tsuda, E. J. Antibiotic. 2001, 54, 541
O
OOMeMe
SNF4435 D
O OOMe
O
O2N
Spectinabilin
Proposed Biosynthesis of SNF4435 C and D
O OOMe
O
O2NSpectinabilin (5)
Double bondsisomerization
Moses, J. E.; Baldwin, J. E.; Marquez, R.; Adlington, R. M.;Cowley, A. R. Org. Lett. 2002, 4, 373120
Ar O
Pyr
HO O
OMe
O
O2N
Proposed BiosyntheticPrecursor (6)
isomerization
Ar O
Pyr
H
8 CON
6
Proposed Biosynthesis of SNF4435 C and D
A
B
8 CON
A BA B
O
O2N
O
O
OMe O
O2N
O
O
OMe
7 8
Proposed Biosynthesis of SNF4435 C and D
Moses, J. E.; Baldwin, J. E.; Marquez, R.; Adlington, R. M.;Cowley, A. R. Org. Lett. 2002, 4, 3731
Biomimetic Synthesis of SNF4435C and D
O2NI
Me3SnSnMe3
Pd(MeCN)2Cl2,O2N
SnMe3
0.1eq Pd(PPh3)4,
2.0eqCsF, 0.2eq CuI,
DMF, 40 oC
IO
8
Conrotatory
HMPA, RT62%
Ar O
H
9 10
Beaudry, C. M.; Trauner, D. Org. Lett. 2005, 7, 447523
O OOMe
O
O2N
O
O
OMeO
O2N
O
O
OMe
Ar
Pyr11
6
7 8
Biomimetic Synthesis of SNF4435C and D
24Beaudry, C. M.; Trauner, D. Org. Lett. 2005, 7, 4475
Reason for 3:1 selectivity
O
PyrH
Ar HO
Ar
H
H
Pyr
6 Disrotatoryelectrocyclization
9 10
Jacobsen,M.F.; Moses,J.E.; Adlington,R.M.; Baldwin,J.E. Org. Lett., 2005, 7 , 247325
Pyr :
O
O
OMe
Ar : pNO2-Ph
Ar
O
Pyr
H
O
Ar
H
PyrH
11 12
Reason for 3:1 selectivity
26
Jacobsen,M.F.; Moses,J.E.; Adlington,R.M.; Baldwin,J.E. Org. Lett., 2005, 7 , 2473
Highlights of this biomimetic synthesis
• The ratio of SNF4435 C and SNF4435 D obtained from the chemical
synthesis agrees with the ratio of the natural abundances of these
compounds.
• This indicates that the 8π-6π electrocyclization cascade may be
completely substrate controlled even in nature and that enzymes
may play an insignificant role – if any – in the biosynthesis of these
compounds from Spectinabillin.
27Beaudry, C. M.; Trauner, D. Org. Lett. 2005, 7, 4475
Few of the Possible Biosynthetic Routes of Spontaneous Assembly
1. Electrocyclizations.
2. Dimerizations.2. Dimerizations.
3. Cascade Reactions
28
Dimerizations : The Biomimetic Synthesis of (-)-Stephacidin B
• Stephacidin B is an optically active, fungal alkaloid isolated from the
fermentation broth of Aspergillius ochraceus in 2001.
• Avrainvillamide had already been isolated from the same fungal species
in 2000.
Qian-Cutrone, J.; Krampitz, K.D.; Shu, Y.Z.; Chang, L.-P.; Lowe, S. E. Stephacidin Antitumor Antibiotics. U.S. Patent 6,291,461, 2001
29
Proposed Mechanism of Dimerization
30
Nussbaum, F.; Angew.Chem.Int.Ed., 2003, 42, 3068
Two Consecutive Michael Additions
31
Nussbaum, F.; Angew.Chem.Int.Ed., 2003, 42, 3068
Proposed biosynthesis of Stephacidin B
32
Nussbaum, F.; Angew.Chem.Int.Ed., 2003, 42, 3068
Dimerization of Avrainvillamide to Stephacidin B
Condition Yield of Stephacidin B ReferencesCondition Yield of Stephacidin B References
Et3N (50eq), MeCN200C, 1-3.5h
>95% conversion by NMR a, b, c
PTLC(SiO2, EtOAc)
15-20%(70-80% recovered 17)
b
DMSO then dried in vacuo
2:1 mixture of 18 and 17 b
a) Herzon, S.B., Myers, A.G. J. Am. Chem. Soc. 2005, 127, 5342b) Baran, P.S., Hafensteiner, B.D., Ambhaikar, N.B., Guerrero, C.A., Gallagher, J.D. J. Am. Chem.
Soc. 2006, 128, 8678.c) Artman III, G.D., Grubbs, A.W., Williams, R.M. J. Am. Chem.Soc. 2007, 129, 6336. 33
Retrodimerization of Stephacidin B
Condition Products
Herzon, S.B., Myers, A.G. J. Am. Chem. Soc. 2005, 127, 534234
Condition Products
Concentration of a MeCN-H2O solution38 °C
2:1 mixture of 17:18
3 Å molecular sieves1:1 DMSO d6:CD3CN
1h, 33°C1:2 mixture of 17:18
SiO2, PTLCPartial retrodimerization
No Yield Reported
Take Home Messages
• The dimerization of the fairly complex nitrone – Avrainvillamide –
seems to occur with great ease under a variety of conditions – basic,
acidic or neutral.
• Retrodimerization of Stephacidin B is also quite facile suggesting • Retrodimerization of Stephacidin B is also quite facile suggesting
that the ready interconversion of the monomer and dimer may be
feasible.
• This suggests that biosynthesis of Stephacidin B may result due to
the inherent reactivity of Avrainvillamide to dimerize.
35
Electrocyclization-Dimerization cascade :Synthesis of Torreyanic Acid
• Torreyanic Acid is a complex polycyclic molecule isolated by Leeand coworkers from various species of the fungus Pestalotiopsis.
• It was proposed that a spontaneous dimerization of a tricyclicprecursor can account for the formation of this heptacycliccompound
J. C. Lee, X. Yang, M. Schwartz, G. A. Strobel, J. Clardy, Chem. Biol. 1995, 2, 72136
Why was a dimerization proposed in the Biosynthesis of Torreyanic Acid?
HO2C
O
OO
O
OO
O
HO2C
O
H
H
Torreyanic Acid
OO
O
O
O
HO2C
OO
O
HO2C
A
B
C D A
B C
D
E
E
37
O
O
O
O
O
HO2C
O
O
O
O
O
O
O
O
HO2C
HO2C
O
O
O
HO2C
A
B
CD
E
A B
ED
C
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
Why was a dimerization proposed in the Biosynthesis of Torreyanic Acid?
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
But the key dimerization step can give 8 different stereoisomers
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
The more energetic transition states
OO
OO
HO2C
21
OO
OO
HO2C
Anti
Syn
OO
OO
HO2C
20
OO
OO
HO2C
Anti
Anti
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
OO
OO
HO2C
22
OO
OO
HO2C
Anti
Syn
OO
OO
HO2C
23
OO
OO
HO2C
Syn
Syn
Model studies of the dimerization
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
Model studies of the dimerization
• The n-pentyl chains are always anti to each other• The dienophile approaches diene from the face opposite to the
epoxide• Chiral epoxide was expected to give a single stereoisomer
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
Figuring out the most favorable transition state
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
O
O
O
O
O
O
O
O
HO2C
HO2CSyn
Syn
23
Biomimetic Synthesis of Torreyanic Acid
O
O
O
O
HO2C
Proposed Biosynthetic Precursor
OH
O
O
O
tBuO2C
Biosynthetic Precursor Mimic
OH
O
O Dess Martin OxidationO
O
C H
O
Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.44
OtBuO2C
Biosynthetic Precursor Mimic (29)
DCM, 23 oCO
C5H11
tBuO2C
O
O
O
C5H11
O
tBuO2C
O
O
O
C5H11
O
tBuO2C
30
31 32
Biomimetic Synthesis of Torreyanic Acid
O
O
O
O
O
O
O
O
tBuO2C
tBuO2C [4+2]
Dimerization
Torreyanic Acid di-tButyl Ester (33)
80% YieldO
O
O
O
O
O
O
O
tBuO2C
tBuO2CAnti
Syn
45Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
48% HF, MeCN
1h, 70%
Torreyanic Acid
O
O
O
O
O
O
O
O
HO2C
HO2C
HO2C
O
OO
O
OO
O
HO2C
O
H
H
Torreyanic Acid
Take Home Messages
• Only 1 out of the 8 possible stereoisomers was predicted and
obtained using chemical synthesis. This product also happens to be
the only isolated stereoisomer of Torreyanic acid.
• This example highlights that enzymatic participation may be minimal
in the biosynthesis of Torreyanic Acid from the proposed biosynthetic
precursor.
46Li, C.; Johnson, R.P.; Porco, J.A.; J. Am. Chem. Soc. 2003, 125, 5095.
Few of the possible biosynthetic routes of spontaneous assembly
1. Electrocyclizations.
2. Dimerizations.2. Dimerizations.
3. Cascade Reactions.
47
Cascade reactionsThe biomimetic synthesis of bisorbicillinoids
O
Me
HO
HO
O
Me
OH
OH
O
Trichodimerol
HO
O
OHO
O
HO
Bisorbicillinol
O
OH
O
• Bisorbicillinoids are dodecapolyketides
isolated from a variety of fungal species.
• It is postulated that they are dimeric
sorbicillin-derived natural products
Abe,N., Murata, T., Hirota, A., Biosci. Biotechnol. Biochem.,1998, 62, 2120Nicolaou, K.C.; Snyder, S.A.; Classics in Total Synthesis II,Wiley-VCH, Weinheim, 2003, chap. 11,
p. 35148
Bisorbibutenolide
O
OH
O
OHO
O
O
OH
Cascade Reactions :The Biomimetic Synthesis of Bisorbicillinoids
O
HO
HO
O
OH
OH
O
Trichodimerol
HO
O
OHO
O
HO
Bisorbicillinol
O
OH
O
Abe,N., Murata, T., Hirota, A., Biosci. Biotechnol. Biochem.,1998, 62, 2120Nicolaou, K.C.; Snyder, S.A.; Classics in Total Synthesis II,Wiley-VCH, Weinheim, 2003, chap. 11,
p. 351
OH
OH
O
Bisorbibutenolide
O
OH
O
O
HO
O
O
OH
Sorbicillin
Abe’s Biosynthetic Hypothesis
OH
OH
O
EnatioselectiveOxidation
Sorbicillin
OH
O
OR
HO
O
R
OH
OR
HO
[O]
35 35'
HO
R
O
O
HOR
O
OH
OH
O
Trichodimerol
HO
O
OHO
O
HO
R
Bisorbicillinol
O
OH
Abe,N., Murata, T., Hirota, A., Biosci. Biotechnol. Biochem.,1998, 62, 2120
Bisorbicillinol : A product of [4+2] dimerization
Abe,N., Murata, T., Hirota, A., Biosci. Biotechnol. Biochem.,1998, 62, 2120
HOR
O
O
OH
OOH
HO
O
R 1
6
5
11
12
23
4
Bisorbicillinol : A product of [4+2] dimerization
O
OH
HO
O
R
O
HO
OH
R
O
11
12
12
3
4
5
6
R =
35 35'
Abe,N., Murata, T., Hirota, A., Biosci. Biotechnol. Biochem.,1998, 62, 2120
Biomimetic Synthesis of Bisorbicillinol
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555 53
HO
O
OH
R
O
HO
O
R
O
OH2 12
5
11
4
3
1
6
Diene Dienophile
Biomimetic Synthesis of Bisorbicillinol
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
HO
O
OH
R
O
HO
O
R
Bisorbicillinol22%
O
OH
1
6
23
45 11
12
R =
In all structures:
Trichodimerol : A product of consecutive Michael Addition – Ketalization reactions
HO
O
O
HO
O
OH
OH
O
Trichodimerol
O
HO
HO
OOH
OO1
2
3
45
Ketalization
OH
36
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
Biosynthetic Hypothesis for Trichodimerol
O
HO
HO
OOH
OO
1
2
3
45
Michael
OH
36
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
O
HO
HO
O
O
O
OHHO
Addition
54
32
1
37
Biosynthetic Hypothesis for Trichodimerol
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
O
OO
HO
OHO
HOHO
5
1
2
3
46
7
89
1011
12
O
OO
HO
51
2
3
46
O
HOHO
7
89
1011
12
H
MichaelAddition
35
Biosynthetic Hypothesis for Trichodimerol
OHO
OO
O
OH
HO
O
O
HO
OH
O
35'
35 35'
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
Biomimetic Synthesis of Trichodimerol
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
Biomimetic synthesis of Trichodimerol
O
O
O
HO
H
Micheal Addition R =
In all structures
OH
O
O
HO
1
2
34
5
6 11
12
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
Micheal Addition R =
O
O
OR
HO
OH
OH
OR
HO
O
O
OR
HO
OH
OH
OR
HO
H
H
1
2
34
5
6
11
12
1 2
34
5
6
11 12
38 38
7
7
8
8
9
9
10
10
Biomimetic synthesis of Trichodimerol
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
Biomimetic synthesis of Trichodimerol
Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.; Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
Take home messages
• Diels-Alder dimerization and Michael addition – Ketalization
cascades must be competing processes as both natural products
are isolated in nature.
• Further rearrangement of these two natural products result in • Further rearrangement of these two natural products result in
formation of other related natural products.
• Enzymatic participation may be limited to the activation of Sorbicillin
63Nicolaou, K.C.; Simonsen, K.B.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, E.; Pitsinos, N.;
Couladouros, E.A.; Angew.Chem. Int. Ed. 1999, 38, 3555
Biomimetic Synthesis can also raise questions about biosynthetic hypotheses.
Biomimetic synthesis of 9,10-deoxytridachione
• 9,10-deoxytridachione wasisolated from the molluskTridachiella diomedea in 1981.
• It seems to be derived from a 6π
electrocyclization of a polyeneprecursor.
Ireland, C.; Faulkner, J.; Tetrahedron, 1981, 37, 233
Biomimetic synthesis of 9,10-deoxytridachione
Moses, J.E.; Adlington, R.M.; Rodriguez, R.I, ; Eade, S.J.; Baldwin, J.E. Chem. Commun., 2005,
1687
Rationalization for the formation of Occelapyrone A
O
OMeO
E E Z
E
O
O
OMe
E Z
Z E
4244
8 -6electrocyclization
cascade
OO
MeO
O
Me
HMe
O
OMe
Occelapyrone A (43)
44
Moses, J.E.; Adlington, R.M.; Rodriguez, R.I, ; Eade, S.J.; Baldwin, J.E. Chem. Commun., 2005,
1687–1689
Rational biomimetic synthesis of Occelapyrones A and B
67Miller, A. K.; Trauner, D. Angew. Chem., Int. Ed. 2005, 44, 4602.
Biomimetic Synthesis of Occelapyrones A and B
• Occelapyrones have been isolated as single enantiomers in nature.
• Biomimetic Synthesis raises several questions:
– Can enzyme mediation be ruled out completely?
– Is the achiral polyene the real biosynthetic precursor?
– Is there an alternate biosynthetic pathway that does not involve
electrocyclization?
68Miller, A. K.; Trauner, D. Angew. Chem., Int. Ed. 2005, 44, 4602.
Conclusions
• While the role of enzymes in biosynthesis cannot be understated, alternate modes of assembly of complex natural products may exist in nature.
• Spontaneous assembly can – to some extent – account for the highly effective exploration of chemical space by nature.
• Biomimetic synthesis can go a long way in bolstering the hypotheses of spontaneous self-assembly.
• However, the conclusions drawn by biomimetic syntheses are at times ambiguous.
69
Acknowledgements
Dr. Babak Borhan
Aman Kulshrestha, Atefeh Garzan, Calvin Grant,
Camille Watson, Carmin Burrell, Chrysoula
Vasileiou, Dan Whitehead, Sing Lee, Kumar
Ashtekar, Mercy Anyika, Roozbeh Yousefi,
Sarah Marshall, Tanya Berbasova, Toyin
Olumulade, Wenjing Wang, Xiaofei Jia,
Xiaouyong Li and Neha
70