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View Online Downloaded by Jacobs University Bremen GGMBH on 26 May 2012 Published on 03 April 2012 on http://pubs.rsc.org | doi:10.1039/C2OB25171J Fig. 6 2D-ROESY interactions for macrocycle (14). 0.01 kcal. mol −1 or less. The results of molecular modelling are in good agreement with the structures suggested by 2D-ROESY experiment and confirm the presence of intramolecular hydrogen bonding interactions (Fig. 7). In solution, macrocycle (14) can assume a minimum energy conformation (14b) which comprises intramolecular hydrogen bonding and π–π stacking interactions. Upon heating (14b) rapid interconversion to the more symmetric conformation (14a) occurs measurable on the NMR time scale. Next, we turned our attention to assessing the reactivity of the unprotected dicarbohydrazides towards the [2 + 2]-cyclocondensation reaction. (2R,3R)-hydrazide (5) and (2S,3S)-hydrazide (6) reacted with terephthaldehyde in methanol (
View Online Table 2 Distances (Å) between some selected atoms for macrocycles (13) and (14) Atoms Macrocycle (13) (Å) Macrocycle (14a) (Å) Macrocycle (14b) (Å) Downloaded by Jacobs University Bremen GGMBH on 26 May 2012 Published on 03 April 2012 on http://pubs.rsc.org | doi:10.1039/C2OB25171J C2–C21 11.83 11.12 16.64 C3–C22 14.02 13.51 17.14 C4–C23 13.56 13.45 15.77 C5–C24 15.56 15.43 13.45 N6–N25 15.90 16.04 12.21 N7–N26 14.02 14.29 10.18 C8–C27 14.99 15.43 9.31 C9–C28 13.79 14.40 7.33 C12–C31 13.25 14.18 6.60 X13–X32 14.09 14.94 5.28 C14–C33 12.51 13.27 6.29 C17–C36 11.49 11.70 9.84 C18–C37 12.06 12.00 12.00 N19–N38 11.59 10.55 13.15 N20–N1 12.42 11.92 15.27 The chirality of the novel macrocycles and their precursors was confirmed by CD-spectroscopy as shown in Fig. 10. All-R macrocycle (14) shows for example a positive Cotton effect with a zero intercept at around 370 nm, whereas its enantiomeric counterpart all-S (16) shows a negative Cotton effect. Similar to trianglimines the observed Cotton effect is a consequence of the interaction of the two aromatic chromophores within the macrocycle. Conclusion In summary, we have synthesised a novel class of chiral nonracemic tetra-carbohydrazide macrocycles starting from commercially available diethyl tartrates. After conversion of the chiral building block to a dihydrazide, reaction with aromatic dialdehydes yielded the novel macrocycles. The macrocyclisation reaction takes place at relatively high concentration of the reactants in MeOH (
Page 1 and 2:
The Development of Novel Antibiotic
Page 3 and 4:
Declaration of Authorship I, Hany N
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Abstract Over the past few decades,
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Chapter 2 Trianglimine Chemistry
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Figure 2.4 Trianglimines 10-12 with
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Abbreviations ACN AcOH Ala Acetonit
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RMS ROESY SjGST TFA THF TLC TMS TOC
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Introduction complete remodel of th
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Introduction following protonation.
Page 19 and 20:
Introduction Lehn and co-workers re
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Introduction Figure 1.8 Generation
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Introduction Figure 1.11 Synthetic
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Introduction Figure 1.13 Generation
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Introduction 1.3.11 Boronic ester e
Page 29 and 30: Introduction References 1. E. Mouli
Page 31 and 32: Introduction 51. B. Shi, M. F. Grea
Page 33 and 34: Introduction Figure 2.2 shows compu
Page 35 and 36: Introduction incorporate β-cyclode
Page 37 and 38: Introduction Trianglamine-Zn(R) 2 c
Page 39 and 40: Introduction 24. J. Gajewy, J. Gawr
Page 41 and 42: Scope of Work Scope of Work In this
Page 43 and 44: Scope of Work can be obtained from
Page 45 and 46: Scope of Work Figure 3.4 Structures
Page 47 and 48: Scope of Work References 1. G. Wrig
Page 49 and 50: Organic & Biomolecular Chemistry Ci
Page 51 and 52: Downloaded by Jacobs University Bre
Page 53 and 54: View Online Downloaded by Jacobs Un
Page 63 and 64: Paper 2 Rapid Commun. Mass Spectrom
Page 65 and 66: Trianglimine formation mechanism by
Page 75 and 76: Paper 3 Org. Biomol. Chem., 2012, 1
Page 79: View Online Downloaded by Jacobs Un
Page 85 and 86: Paper 4 Chem. Eur. J., 2012, submit
Page 87 and 88: (4R,5R)- and (4S,5S)-dimethyl-2,2-d
Page 89 and 90: that two distinct conformational is
Page 91 and 92: the thimble was recharged with fres
Page 93 and 94: Paper 5 Rapid Commu. Mass Spectrom.
Page 95 and 96: INTRODUCTION No single class of dru
Page 97 and 98: EXPERIMENTAL All the solvents and r
Page 99 and 100: (b) Refluxing macrocycles 5, 6 and
Page 101 and 102: Scheme 1. Graphical representation
Page 103 and 104: Figure 1. A plot of relative intens
Page 105 and 106: In contrast, formation of library m
Page 107 and 108: Figure 5. Generated dynamic library
Page 109 and 110: macrocycle 32 from the dynamic libr
Page 111 and 112: The polar carbamate group participa
Page 113 and 114: [2] WHO World health report 2003. h
Page 115 and 116: [32] B. Lienard, N. Selevsek, N. Ol
Page 117 and 118: FULL PAPER Synthesis and ESI-MS Com
Page 119 and 120: ability of the technique to provide
Page 121 and 122: aimed at assessing molecular recogn
Page 123 and 124: Paper 7 manuscript Synthesis, self-
Page 125 and 126: 2 Similar to the case of trianglimi
Page 127 and 128: 4 Receptor 7 showed enhanced recogn
Page 129 and 130: 6 The newly synthesized receptors s
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8 27. Nour, H. F.; Hourani, N.; Kuh
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120| P a g e Appendix
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Supplementary Information: Suppleme
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Supplementary Material (ESI) for Or
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Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Monitoring the [3+3]-cyclocondensat
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Monitoring the cyclocondensation re
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Product ions appeared as [M+H] + Fi
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Scheme 1. Assigned higher oligomers
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Supplementary Information: Synthesi
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Scheme 4. Proposed fragmentation me
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DMSO Figure 1. 1 H-NMR spectrum for
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Figure 6. 13 C-NMR spectrum for (4S
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Intens. 7 x10 1.5 200.7 1.0 0.5 0.0
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Intens. 7 x10 200.7 1.5 1.0 0.5 0.0
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Intens. 4 x10 577.2 2.0 1.5 1.0 451
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HN N O O R R NH O O N N HN R O O O
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Intens. 5 x10 727.2 2.0 1.5 1.0 O O
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Intens. 5 x10 697.1 1.5 1.0 728.2 0
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O O O O HN N O O NH N HN N O O NH N
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Figure 38. 1 H-NMR spectrum for mac
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Intens. 5000 276.8 4000 3000 2000 1
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Intens. 7 x10 599.1 1.5 1.0 0.5 0.0
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(a) HN N O O NH O O N (b) HN N O NH
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Scheme 11. Proposed fragmentation m
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Scheme 14. Proposed fragmentation m
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Intens. 4 x10 550.9 3 2 1 0 500 100
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Figure 68. 2D-ROESY spectrum for ma
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Supplementary Information: Novel sy
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Intens. 6 x10 0.8 0.6 0.4 240.9 459
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Figure 9. 1 H-NMR spectrum for macr
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Intens. 5 x10 1.5 968.1 1.0 0.5 813
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Intens. 5 x10 897.4 4 2 335.3 707.3
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Scheme 3. Suggested fragmentation m
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Molecular modelling data for the co
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Figure 1. 1 H NMR spectrum for dica
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Intens. 2000 1493.6091 Host-Guest 1
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Intens. [%] 100 775.3 80 388.1 60 4
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Intens. 600 N HN O O 467.1916 400 O
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Intens. 6000 5000 HN N O O O O NH N
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Table 1. High resolution ESI-TOF da
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i Figure 1. 1 H NMR spectrum for ma
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i Figure 5. 1 H NMR spectrum for ma
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i j Figure 9. 1 H NMR spectrum for
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i Figure 13. DEPT-135 spectrum for
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Scheme 1. General mechanism of frag
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Intens. [%] 100 80 60 40 20 0 O H N
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Intens. [%] 100 1131.3 80 60 40 20
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Intens. 1500 1528.6088 1000 500 150
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Intens. [%] 100 80 60 40 Free guest
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Intens. 4 x10 1085.3575 1.25 1.00 0
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Intens. [%] 100 80 Free guest 586.1
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Synthesis, self-assembly and ESI-MS
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O O HN NH HN O O NH HN O 11 O NH O
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O O HN NH HN O O NH HN O 9 O NH O O
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H 2 O DMSO DMSO Figure 6. 1 H-NMR a
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Intens. 5 x10 5 -MS 487.1588 4 3 2
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Intens. -MS 6 x10 0.8 0.6 0.4 0.2 1
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Intens. -MS 6 x10 O O 350.9 1.5 1.0
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Intens. [%] 100 -MS 486.9 Exact str
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Intens. [%] -MS 100 486.9 80 60 975
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Intens. [%] +MS 100 80 517.2 Exact
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Intens. [%] 100 80 60 +MS 388.1 775
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Intens. [%] 100 +MS 517.2 Exact str
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Intens. [%] 100 80 +MS 1031.4939 7
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Intens. [%] 100 +MS 517.2 Exact str
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Intens. [%] 100 -MS 2 586.1 80 60 4
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Intens. [%] 100 -MS 2 875.2 Exact s
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Table 1. High resolution ESI-TOF/MS
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274 | P a g e
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276 | P a g e
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4. H. Nour, A. López-Periago, N. K
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