the development of novel antibiotics using chemical evolution hani fathi nour assistant researcher...
TRANSCRIPT
![Page 1: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/1.jpg)
The Development of Novel Antibiotics Using Chemical Evolution
Hani Fathi Nour
Assistant ResearcherNational Research Centre, Egypt
M.Sc. Cairo University 2007DAAD scholarship holder 2008
Jacobs University Bremen, Germany
Thesis Committee
1. Prof. Dr. Nikolai Kuhnert2. Prof. Dr. Marcelo Fernández-Lahore3. Prof. Dr. Sijbren Otto
Supervisor: Prof. Dr. Nikolai Kuhnert
©
![Page 2: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/2.jpg)
2An overview and objectives
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
![Page 3: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/3.jpg)
3Dynamic versus traditional combinatorial chemistry
Traditional combinatorial chemistry
+
Dynamic combinatorial chemistry (DCC)
+++++++++
![Page 4: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/4.jpg)
4Chemistry of trianglimines
1
![Page 5: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/5.jpg)
5Synthesis of highly functionalised trianglimines
O
Br
FHNu
O
Br
Nu
BOH
HO
O
Nu
O
O
Nu
O
O
H2N NH2
H2N
H2N
NuO O
NH2
NH2
• Nucleophilic aromatic substitution
• Suzuki-coupling reaction
• Condensation
O
O
Nu
C3-Symmetrical Unsymmetrical
![Page 6: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/6.jpg)
6Separation of trianglimine regioisomers
N N
NN
N N
N
OO
N
OO
N
O
O
N N
NN
N N
N
OO
N
OO
N
OO
2
3
![Page 7: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/7.jpg)
7Monitoring the [3+3]-cyclocondensation reaction by ESI/TOF MS
290.2611 747.4909 893.59320.0
Intens.
200 400 600 800 1000 1200
443.2801
637.3991
0.5
1.0
1.5
5x10
m/z
326.1287
443.2808
637.3997
777.5626 893.5943
0.00
0.25
0.50
0.75
1.00
1.25
5x10
Intens.
200 400 600 800 1000 1200 m/z
Intens.
637.4081
0
1
2
3
4
200 400 600 800 1000 1200 m/z
1 h
2 h
3 h
N N
OHCN
H2N
C28H34N4O442
N
N
N N
N
N
636C42H48N6
4
1
![Page 8: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/8.jpg)
8Monitoring the [3+3]-cyclocondensation reaction by ESI/TOF MS
290.2612327.2543 347.1759
425.2714
443.2798
637.4026
0.0
0.5
1.0
1.5
2.0
4x10
Intens.
250 300 350 400 450 500 550 600 650 m/z
N
N
N
N
7N
NN
NH2
O
8
NN
OO
6
N
NH2
N
H2N
5 NN
NN
NN
9
1 h
425.2776
637.4079
0.0
0.5
1.0
1.5
2.0
5x10
Intens.
200 400 600 800 1000 1200 m/z
N
N
N
N
7
NN
NN
NN
9
12 h
9
7
![Page 9: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/9.jpg)
9Conformation of trianglimines
2
![Page 10: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/10.jpg)
10
N N
NN
N N
O
O
O
N N
NN
N N
O
O
O
N N
NN
N N
N
N
N
NN
N
N N
NN
N N
N
OO
N
OO
N
OO
N N
NN
N N
N
OO
N
OO
N
O
O
10 (37%) 2 (31%)
11 (22%) 3 (4%)
12 (11%)
![Page 11: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/11.jpg)
11
N N
NN
N N
N
N
N
N
N
NO
OO
O
OO
N N
NN
N N
N
N
N
N
OO
OO
NNO
O
NH HN
HNNH
NH HN
O
O
O NH HN
HNNH
NH HN
O
O
O
NaBH4 THF/MeOH
N N
NN
N N
NH HN
HNNH
NH HN
13 (35%) 14 (10%)
15 (99%) 16 (99%)
![Page 12: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/12.jpg)
14
13
12
![Page 13: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/13.jpg)
Paper 1 13
![Page 14: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/14.jpg)
Probing the mechanism and dynamic reversibility of trianglimine formation 14
![Page 15: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/15.jpg)
Exact mechanism for formation of trianglimines
17
18 19
20
21 22
1
15
![Page 16: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/16.jpg)
Exact mechanism for formation of trianglimines
How were the pyramids built?
N NH2
O
N NH2
N
NH2
N NH2
N
N O
N NH2
H2NN
N N
N N
NN
N N
Who revealed the stepwise mechanism of trianglimines?
A PhD student in Kuhnert group, Hany Nour
16
![Page 17: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/17.jpg)
Dynamic reversibility of trianglimines
N N
N N
N N
N
N
N
OO
N
NO
O
NO
O
13
N N
N N
N N
O
O
O
15
N
N
OO
O
OO
O
O
H2N
H2N
NH2
NH2
N
NO
O
O O
H2N NH2
N
NO
O
O
O
O
O
O
NH2
NH2
H2N
H2N
H2N NH2
OO O
17
![Page 18: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/18.jpg)
N
N
OO
O
O
OO
O
H2N
H2N
N
NO
O
O O
H2N NH2
N
NO
O
O
O
O
O
O
OO O
NH2
NH2
H2N
H2N
H2N NH2
NH2
NH2
N N
N N
N N
O
O
O
15
N N
N N
N N
N
N
N
OO
N
NO
O
NO
O
13
18
![Page 19: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/19.jpg)
N
NO
O
O
O 24
O
O
O
25
H2N NH2
23
N N
N N
N N
O
O
O
15
N N
N N
N N
O
O N
NO
O
26 New
N N
N N
N N
NO
NO
O
N
NO
O
27 New
1 : 1 : 2
19
![Page 20: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/20.jpg)
Paper 2 20
![Page 21: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/21.jpg)
Trianglimine
Somet
hing e
lse
Nothing is more difficult, and therefore more precious, than to be able to decide (Napoleon Bonaparte)
Jetzt muss ich mich entscheiden!
21
![Page 22: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/22.jpg)
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
28 2923
30 31
22
![Page 23: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/23.jpg)
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
32
33
34
23
![Page 24: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/24.jpg)
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
35 36 (57%)
37 38 (63%)
35 39 (88 %)
37 40 (70 %)
24
![Page 25: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/25.jpg)
47, 4948, 50
4144
4245
4346
44
41-43 44-46
47-48 49-50
25
![Page 26: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/26.jpg)
48
48
26
![Page 27: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/27.jpg)
X-Ray structure by Gawroński et al .
Conformation of Tetra-carbohydrazide cyclophanes
48a
48b
27
![Page 28: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/28.jpg)
Structure of Tetra-carbohydrazide cyclophanes versus structure of trianglimines
51
52
33
53
28
![Page 29: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/29.jpg)
Conformation of non-protected Tetra-carbohydrazide cyclophanes 29
![Page 30: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/30.jpg)
Paper 3 30
![Page 31: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/31.jpg)
54 55 (88%)
56 57 (77%)
58 3558 (55%)
58 3759 (56%)
60 61
62
31
![Page 32: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/32.jpg)
259.1319
539.2550
775.4022
1033.5420
0.0
0.5
1.0
1.5
2.0
5x10
Intens.
500 1000 1500 2000 2500 m/z
517.2706
63
32Self-assembled dioxolane dihydrazides
![Page 33: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/33.jpg)
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
64, X = O (97 %)65, X = NPh (99 %)
66, X = O (94 %)67, X = NPh (99 %)
68, X = O (98 %)69, X = NPh (99 %)
33
![Page 34: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/34.jpg)
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
70, X = O (88 %)71, X = NPh (89 %)
65
34
![Page 35: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/35.jpg)
Manuscript 4, submitted to Chem. Eur. J. 35
![Page 36: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/36.jpg)
O O
NHO
HNO NH2H2N
58
O O
NHO
HNO NH2H2N
36
O
O O
72
N
OO
73
O
O
NHO NH2
HNOH2N
A
HNOH2N
NHO NH2
D
O
C
O
72 73
74 75
36
![Page 37: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/37.jpg)
O O
NHO
HNO NH2H2N
58
O O
NHO
HNO NH2H2N
36
O
O O
72
N
OO
73
O
O
NHO NH2
HNOH2N
A
HNOH2N
NHO NH2
D
O
C
O
76 77
78 79
37
![Page 38: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/38.jpg)
72 73
74 75
NHO N
HNO
HNON
NHO N
N
72B B
D
D
NHO N
HNO
HNON
NHO N
N
73C C
D
D
NHO N
HNO
HNON
NHO N
N
74B B
A
A
38
![Page 39: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/39.jpg)
76 77
78 79
NHO N
HNO
HNON
NHO N
N
72B B
D
D
NHO N
HNO
HNON
NHO N
N
73C C
D
D
NHO N
HNO
HNON
NHO N
N
74B B
A
A
39
![Page 40: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/40.jpg)
72
73
74
75
76
77
78
79
72
737475767778
79
OO
NHHNN NH2O O
X
O
OO
NHHNN NO O
X
O
Y
O
O
O
NH
NHN
H2N
O
O
X
NHN
O
O
HNNH2
O
O
R1 R2R2R1
86 R1 = R2 = H, X = Y = O87 R1 = R2 = H, X = Y = NPh88 R1 = R2 = (CH2)5, X = Y = O89 R1 = R2 = H, X = NPh, Y = O90 R1 = R2 = (CH2)5, X = NPh, Y = O
80 R1 = R2 = H, X = O81 R1 = R2 = H, X = NPh82 R1 = R2 = (CH2)5, X = O
80-82 86-90
83 R1 = R2 = H, X = O84 R1 = R2 = H, X = NPh85 R1 = R2 = (CH2)5, X = O
83-85 R1
R2
R1
R2
40
![Page 41: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/41.jpg)
76
72
80 86
47 83
41Mechanism of Tetra-carbohydrazide cyclophanes formation
![Page 42: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/42.jpg)
O O
NHO
HNO NH2H2N
91
N
O O
O O
NHO
HNO NH2H2N
36
O
O O
72
N
OO
73
O
O
NHO NH2
HNOH2N
A
HNOH2N
NHO NH2
D
O
C
O
92 93
94 95
42
![Page 43: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/43.jpg)
O O
NHO
HNO NH2H2N
91
N
O O
O O
NHO
HNO NH2H2N
36
O
O O
72
N
OO
73
O
O
NHO NH2
HNOH2N
A
HNOH2N
NHO NH2
D
O
C
O
96 97
98 99
43
![Page 44: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/44.jpg)
(98)
(95)
(93)
(99)
(97)
(92)
(96) (94)
Frag Frag
NHO N
HNO
HNON
NHO N
N
95B C
D
D
NHO N
HNO
HNON
NHO N
N
93
A
B B
D
NHO N
HNO
HNON
NHO N
N
97
A
B C
D
44ESI-TOF/MS spectrum for a small DCL of Tetra-carbohydrazide cyclophanes
![Page 45: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/45.jpg)
O
NH
O OHN
OHO
O
NH
NH2
OHN
O
NH
OHN
OH
OHN
OHO
O O
NH
NH2
OHN
O
NH
OHN
OH
O
NH
NH2
O OHN
O
NH
OHN
OH
100 AcNH-D-Ala-D-Glu-L-Lys-D-Ala-D-Ala-Gly-COOH 101 AcNH-D-Glu-L-Lys-D-Ala-D-Ala-Gly-COOH
102 AcNH-L-Lys-D-Ala-D-Ala-Gly-COOH
45Oligopeptides which mimic bacterial cell wall structure
![Page 46: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/46.jpg)
Three self-assembled molecules of guest 102
Four self-assembled molecules of guest 102
NHO N
HNO
HNON
NHO N
N
95/102
B C
D
D
NHO N
HNO
HNON
NHO N
N
93/102
A
B B
D
NHO N
HNO
HNON
NHO N
N
97/102
A
B C
D
46
![Page 47: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/47.jpg)
NHO N
HNO
HNON
NHO N
N
97/102
A
B C
D
NHO N
HNO
HNON
NHO N
N
97
A
B C
D
102
47MS/MS spectrum for host/guest complex 97/102
![Page 48: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/48.jpg)
Paper 5, accepted manuscript in RCM
48
![Page 49: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/49.jpg)
Paper 6, tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles 49
![Page 50: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/50.jpg)
36 R1 = R2 = H 54 R1 = R2 = CH3
58 R1 + R2 = (CH2)5
105-110
105 R1 = R2 = H, X = O (94%) 106 R1 = R2 = H, X = CH2 (99%)107 R1 = R2 = CH3, X = O (89%)
108 R1 = R2 = CH3, X = CH2 (90%)
109 R1 + R2 = (CH2)5, X = O (97%)110 R1 + R2 = (CH2)5, X = CH2 (99%)
105-110
50Synthesis of tetra-(hydrazinecarboxamide) cyclophanes
103 X = O104 X = CH2
![Page 51: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/51.jpg)
105a syn/anti
105b syn/syn 105c anti/anti
107
51
![Page 52: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/52.jpg)
52Paper 6, manuscript will be submitted to Eur. J. Org. Chem.
![Page 53: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/53.jpg)
Paper 7, bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors 53
![Page 54: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/54.jpg)
111, R1 = R2 = R3 = H, R4 = OCH3 112, R1 + R2 = (CH2)5, R3 = H, R4 = OCH3 113, R1 = R2 = H, R3 = R4 = OCH3 114, R1 = R2 = R3 = H, R4 = N(CH3)2
OO
NHO
HNO NH2H2N
OO
NHO
HNO NH2H2N
OO
NHO
HNO NH2H2N
R R R R S S
36 58 38
OO
NHO
HNO NHHN
R R
ONH
OHN
R2R1
R3
R4 R4
R3
OO
NHO
HNO NHHN
S S
ONH
OHN
R2R1
R3
R4 R4
R3
115, R1 = R2 = R3 = H, R4 = OCH3 116, R1 = R2 = H, R3 = R4 = OCH3 117, R1 = R2 = R3 = H, R4 = N(CH3)2
111
112
113
114
115
116
117
78%
74%
93%
89%
96%
99%
93%
54Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
![Page 55: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/55.jpg)
55Conformation of bis-N-substituted hydrazinecarboxamides
![Page 56: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/56.jpg)
111
56
![Page 57: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/57.jpg)
57
![Page 58: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/58.jpg)
111D-(‒)-quinic acid
58
![Page 59: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/59.jpg)
O
NH
O OHN
OHO
O
NH
NH2
OHN
O
NH
OHN
OH
100 AcNH-D-Ala-D-Glu-L-Lys-D-Ala-D-Ala-Gly-COOH
OO
NHO
HNO NHHN
R R
ONH
OHN
OO
111
OO
NHO
HNO NHHN
R R
ONH
OHN
OO
113
OO
OO
NHO
HNO NHHN
R R
ONH
OHN 114
N N
59
![Page 60: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/60.jpg)
111113100
113114100
111113114100
60Selective recognition of bis-N-substituted hydrazinecarboxamides
![Page 61: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/61.jpg)
61Paper 7, manuscript will be submitted to Tetrahedron
![Page 62: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/62.jpg)
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
What are antibiotics?
How do antibiotics attack bacteria?
How do bacteria resist antibiotics?
Aim of thesis
Dynamic versus traditional combinatorial chemistry
Generation of a dynamic combinatorial library ( DCL ) from trianglimine macrocycles
Synthesis of Tetra-carbohydrazide cyclophanes as a novel class of macrocycles
Generation of a DCL from Tetra-carbohydrazide cyclophanes
ESI-TOF/MS recognition of Tetra-carbohydrazide cyclophanes to oligopeptides
Tetra-(hydrazinecarboxamide) cyclophanes, a novel class of polyamide macrocycles
Bis-N-substituted hydrazinecarboxamides, a novel class of two armed receptors
Conclusion
62
![Page 63: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/63.jpg)
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Highly functionalised trianglimine regioisomers were successfully synthesized and purified.
Mechanism of trianglimine formation was investigated and dynamic reversibility was confirmed.
A novel class of chiral tetra-carbohydrazide cyclophanes was synthesized.
Tetra-carbohydrazide cyclophanes showed dynamic exchange with generation of a small DCL.
Three members in the DCL showed recognition to oligopeptides as confirmed by ESI-TOF/MS.
A novel class of polyamide tetra-(hydrazinecarboxamide) cyclophanes was synthesized.
A novel class of two armed bis-N-substituted hydrazinecarboxamide receptors was synthesized.
The novel bis-N-substituted hydrazinecarboxamide receptors showed unique self-assembly.
Most importantly, this work is just a start for an endless collaboration with Prof. Kuhnert.
Conclusion 63
![Page 64: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/64.jpg)
64
![Page 65: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/65.jpg)
65Possible applications of the novel tetra-(hydrazinecarboxamide) cyclophanes
NHO N
HNO
HNON
NHO N
NNH
O NHN
O
HNON
NHO N
NM
M
![Page 66: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/66.jpg)
References
J. Gawroński, H. Kołbon, M. Kwit, A. Katrusiak, J. Org. Chem., 2000, 65, 5768. N. Kuhnert, A. López-Periago, G. Rossignolo, Org. Biomol. Chem., 2005, 3, 524. N. Kuhnert, A. López-Periago, G. Rossignolo, Org. Biomol. Chem., 2003, 1, 1157. N. Kuhnert, N. Burzlaff, C. Patel and A. López-Periago, Org. Biomol. Chem., 2005, 3, 1911. N. Kuhnert, A. López-Periago, G. Rossignolo, Org. Biomol. Chem., 2005, 3, 524. N. Kuhnert, D. Marsh, D. Nicolau, Tetrahedron: Asymm., 2007, 18, 1648. N. Kuhnert, B. Tang, Tetrahedron Lett., 2006, 47, 2985. S. Nielsen, M. Larsen, T. Boesen, K. Schønning, H. Kromann, J. Med. Chem., 2005, 48, 2667. J. Stewart, J. Comput. Chem., 1989, 10, 221. H. Nour, M. Matei, B. Bassil, U. Kortz, N. Kuhnert, Org. Biomol. Chem., 2011, 9, 3258. A. Dahlgren, J. Brånalt, I. Kvarnström, I. Nilsson, D. Musilc, B. Samuelsson, Bioorg. Med. Chem., 2002,
10, 1567. H. Nour, A. López-Periago, N. Kuhnert, Rapid Comm. Mass Spectrom., 2012, 26, 1070. H. Nour, N. Hourani, N. Kuhnert, Org. Biomol. Chem., 2012, 10, 4381. H. Nour, A. Golon, A. Le-Gresley, N. Kuhnert, Chem. Eur. J., 2012, submitted manuscript. H. Nour, T. Islam, M. Fernández-Lahore, N. Kuhnert, Rapid Comm. Mass Spectrom., 2012, accepted
manuscript. Molecular modeling was carried out using HyperChem software (Release 8.0). Hypercube, Inc., 1115 NW
4th Street, Gaineville, F1 32601 USA. Trial, version from http://www.hypercube.com P. Skowronek, M. Kuncewicz, M. Brzostowska, A. Janiak, U. Rychlewska, J. Gawroński, Tetrahedron:
Asymm., 2012, 23, 300. S. Zimmerman, C. VanZyl, J. Am. Chem. Soc., 1987, 109, 7894.
66
![Page 67: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/67.jpg)
M. Hegab, A.-S. Abdel-fattah, N. Yousef, H. Nour, A. Mostafa, M. Ellithey, Synthesis, X-ray structure, and pharmacological activity of some 6,6-disubstituted chromeno[4,3-b]- and chromeno[3,4-c]-quinolines, Arch. Pharm. Chem. Life Sci., 2007, 340, 396.
M. Hegab, N. Yousef, H. Nour, M. Ellithey, Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromen-3-carboxaldehyde derivatives, Acta. Pharm., 2008, 58, 15.
H. Nour, M. Matei, B. Bassil, U. Kortz, N. Kuhnert, Synthesis of tri-substituted biaryl based trianglimines: formation of C3-symmetrical and non-symmetrical regioisomers, Org. Biomol. Chem., 2011, 9, 3258.
H. Nour, A. López-Periago, N. Kuhnert, Probing the mechanism and dynamic reversibility of trianglimine formation using real-time electrospray ionization time-of-flight mass spectrometry, Rapid Commun. Mass Spectrom., 2012, 26, 1070.
H. Nour, N. Hourani, N. Kuhnert, Synthesis of novel enantiomerically pure tetra-carbohydrazide cyclophane macrocycles, Org. Biomol. Chem., 2012, 10, 4381.
H. Nour, A. Golon, A. Le-Gresley, N. Kuhnert, Novel synthesis of enantiomerically pure dioxaspiro[4.5]decane tetra-carbohydrazide cyclophane macrocycles, Chem. Eur. J., 2012, submitted manuscript.
H. Nour, T. Islam, M. Fernández-Lahore, N. Kuhnert, Probing the dynamic reversibility and generation of dynamic combinatorial libraries in the presence of bacterial model oligopeptides as templating guests of tetra-carbohydrazide macrocycles using electrospray mass spectrometry, Rapid Commun. Mass Spectrom., 2012, accepted manuscript.
H. Nour, A. Golon, N. Kuhnert, Synthesis of novel chiral tetra-(hydrazinecarboxamide) cyclophane macrocycles, Eur. J. Org. Chem., 2012, manuscript.
H. Nour, A. Golon, T. Islam, M. Fernández-Lahore, N. Kuhnert, Synthesis, self-assembly and ESI-MS complexation studies of novel chiral bis-N-substituted-hydrazinecarboxamide receptors, manuscript.
N. Kuhnert, F. Dairpoosh, R. Jaiswal, M. Matei, S. Deshpande, A. Golon, H. Nour, H. Karaköse, N. Hourani, Hill coefficients of dietary polyphenolic enzyme inhibitiors: can beneficial health effects of dietary polyphenols be explained by allosteric enzyme denaturing?, J. Chem. Biol., 2011, 4, 109.
Publications
67
![Page 68: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/68.jpg)
68Acknowledgement
Prof. Dr. Nikolai KuhnertProf. Dr. Marcelo Fernández-LahoreProf. Dr. Sijbren OttoMrs. Anja Müller
![Page 69: The Development of Novel Antibiotics Using Chemical Evolution Hani Fathi Nour Assistant Researcher National Research Centre, Egypt M.Sc. Cairo University](https://reader035.vdocuments.net/reader035/viewer/2022062404/551a8b36550346b52d8b5b38/html5/thumbnails/69.jpg)
Fragen?
Fragen kostet nichts – aber Antworten ist teuer