The Development of Novel Antibiotics Using ... - Jacobs University

More documents

Recommendations

Info

[17] N. Kuhnert, A. Lopez-Periago. Synthesis of novel chiral non-racemic substituted trianglimine and trianglamine macrocycles. Tetrahedron Lett. 2002, 43, 3329. [18] N. Kuhnert, A. Lopez-Periago, G. Rossignolo. The synthesis and conformation of oxygenated trianglimine macrocycles. Org. Biomol. Chem. 2005, 3, 524. [19] N. Kuhnert, G. Rossignolo, A. Lopez-Periago. The synthesis of trianglimines: on the scope and limitations of the [3+3]-cyclocondensation reaction between (1R,2R)-diaminocyclohexane and aromatic dicarboxaldehydes. Org. Biomol. Chem. 2003, 1, 1157. [20] N. Kuhnert, C. Straßnig, A. Lopez-Periago. Synthesis of novel enantiomerically pure trianglimine and trianglamine macrocycles. Tetrahedron: Asymmetry 2002, 13, 123. [21] N. Kuhnert, C. Patel, F. Jami. Synthesis of chiral non-racemic polyimine macrocycles from cyclocondensation reactions of biaryl and terphenyl based dicarboxaldehydes and (1R,2R)- diaminocyclohexane. Tetrahedron Lett. 2005, 46, 7575. [22] N. Kuhnert, B. Tang. Synthesis of diastereomeric trianglamine-β-cyclodextrin-[2]- catenanes. Tetrahedron Lett. 2006, 47, 2985. [23] N. Kuhnert, D. Marsh, D. Nicolau. The application of quasienantiomeric trianglamine macrocycles as chiral probes for anion recognition in ion trap ESI mass spectrometry. Tetrahedron: Asymmetry 2007, 18, 1648. [24] H. Nour, M. Matei, B. Bassil, U. Kortz, N. Kuhnert. Synthesis of tri-substituted biaryl based trianglimines: formation of C 3 -symmetrical and non-symmetrical regioisomers. Org. Biomol. Chem. 2011, 9, 3258. [25] H. Nour, A. Lopez-Periago, N. Kuhnert. Probing the mechanism and dynamic reversibility of trianglimine formation using real-time electrospray ionization time-of-flight mass spectrometry. Rapid Comm. Mass Spectrom. 2012, 26, 1070. [26] H. Nour, N. Hourani, N. Kuhnert. Synthesis of novel enantiomerically pure tetracarbohydrazide cyclophane macrocycles. Org. Biomol. Chem. 2012, 10, 4381. [27] 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. [28] S.-A. Poulsen. Direct screening of a dynamic combinatorial library using mass spectrometry. J. Am. Soc. Mass. Spectrom., 2006, 17, 1074. [29] Release 8.0. Hypercube, Inc., 1115NW 4th Street, Gaineville, FL 32601, USA. Available: http://www.hypercube.com. [30] J. Stewart. Optimization of parameters for semiempirical methods. II. Applications. J. Comput. Chem. 1989, 10, 221. [31] Z. Ziora, N. Wimmer, R. New, I. Toth. Design and synthesis of lipopeptides and lipopeptidomimetics as novel potential drugs. Peptide Sci. 2010, 47, 214. 21 | P a g e
[32] B. Lienard, N. Selevsek, N. Oldham, C. Schofield. Combined mass spectrometry and dynamic chemistry approach to identify metalloenzyme inhibitors. ChemMedChem. 2007, 2, 175. [33] S.-A. Poulsen, L. Bornaghi. Fragment-based drug discovery of carbonic anhydrase II inhibitors by dynamic combinatorial chemistry utilizing alkene cross metathesis. Bioorg. Med. Chem. 2006, 14, 3275. [34] T. Bunyapaiboonsri, H. Ramstroem, O. Ramstroem, J. Haiech, J.-M. Lehn. Generation of bis-cationic heterocyclic inhibitors of bacillus subtilis HPr Kinase/Phosphatase from a ditopic dynamic combinatorial library. J. Med. Chem. 2003, 46, 5803. [35] A. Dahlgren, J. Brånalt, I. Kvarnström, I. Nilsson, D. Musilc, B. Samuelsson. Synthesis of potential thrombin inhibitors. Incorporation of tartaric acid templates as P2 proline mimetics. Bioorg. Med. Chem. 2002, 10, 1567. 22 | P a g e
Page 1 and 2:
The Development of Novel Antibiotic
Page 3 and 4:
Declaration of Authorship I, Hany N
Page 5 and 6:
Abstract Over the past few decades,
Page 7 and 8:
Chapter 2 Trianglimine Chemistry
Page 9 and 10:
Figure 2.4 Trianglimines 10-12 with
Page 11 and 12:
Abbreviations ACN AcOH Ala Acetonit
Page 13 and 14:
RMS ROESY SjGST TFA THF TLC TMS TOC
Page 15 and 16:
Introduction complete remodel of th
Page 17 and 18:
Introduction following protonation.
Page 19 and 20:
Introduction Lehn and co-workers re
Page 21 and 22:
Introduction Figure 1.8 Generation
Page 23 and 24:
Introduction Figure 1.11 Synthetic
Page 25 and 26:
Introduction Figure 1.13 Generation
Page 27 and 28:
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 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
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 77 and 78: View Online Downloaded by Jacobs Un
Page 81 and 82: View Online Table 2 Distances (Å)
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: [2] WHO World health report 2003. h
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
Page 131 and 132: 8 27. Nour, H. F.; Hourani, N.; Kuh
Page 133 and 134: 120| P a g e Appendix
Page 135 and 136: Supplementary Information: Suppleme
Page 137 and 138: Supplementary Material (ESI) for Or
Page 153 and 154: Monitoring the [3+3]-cyclocondensat
Page 155 and 156: Monitoring the cyclocondensation re
Page 157 and 158: Product ions appeared as [M+H] + Fi
Page 159 and 160: Scheme 1. Assigned higher oligomers
Page 161 and 162: Supplementary Information: Synthesi
Page 163 and 164: Scheme 4. Proposed fragmentation me
Page 165 and 166:
DMSO Figure 1. 1 H-NMR spectrum for
Page 167 and 168:
Figure 6. 13 C-NMR spectrum for (4S
Page 169 and 170:
Intens. 7 x10 1.5 200.7 1.0 0.5 0.0
Page 171 and 172:
Intens. 7 x10 200.7 1.5 1.0 0.5 0.0
Page 173 and 174:
Intens. 4 x10 577.2 2.0 1.5 1.0 451
Page 175 and 176:
HN N O O R R NH O O N N HN R O O O
Page 177 and 178:
Intens. 5 x10 727.2 2.0 1.5 1.0 O O
Page 179 and 180:
Intens. 5 x10 697.1 1.5 1.0 728.2 0
Page 181 and 182:
O O O O HN N O O NH N HN N O O NH N
Page 183 and 184:
Figure 38. 1 H-NMR spectrum for mac
Page 185 and 186:
Intens. 5000 276.8 4000 3000 2000 1
Page 187 and 188:
Intens. 7 x10 599.1 1.5 1.0 0.5 0.0
Page 189 and 190:
(a) HN N O O NH O O N (b) HN N O NH
Page 191 and 192:
Scheme 11. Proposed fragmentation m
Page 193 and 194:
Page 195 and 196:
Scheme 14. Proposed fragmentation m
Page 197 and 198:
Intens. 4 x10 550.9 3 2 1 0 500 100
Page 199 and 200:
Figure 68. 2D-ROESY spectrum for ma
Page 201 and 202:
Supplementary Information: Novel sy
Page 203 and 204:
Intens. 6 x10 0.8 0.6 0.4 240.9 459
Page 205 and 206:
Figure 9. 1 H-NMR spectrum for macr
Page 207 and 208:
Page 209 and 210:
Intens. 5 x10 1.5 968.1 1.0 0.5 813
Page 211 and 212:
Intens. 5 x10 897.4 4 2 335.3 707.3
Page 213 and 214:
Scheme 3. Suggested fragmentation m
Page 215 and 216:
Page 217 and 218:
Molecular modelling data for the co
Page 219 and 220:
Figure 1. 1 H NMR spectrum for dica
Page 221 and 222:
Intens. 2000 1493.6091 Host-Guest 1
Page 223 and 224:
Intens. [%] 100 775.3 80 388.1 60 4
Page 225 and 226:
Intens. 600 N HN O O 467.1916 400 O
Page 227 and 228:
Intens. 6000 5000 HN N O O O O NH N
Page 229 and 230:
Table 1. High resolution ESI-TOF da
Page 231 and 232:
i Figure 1. 1 H NMR spectrum for ma
Page 233 and 234:
i Figure 5. 1 H NMR spectrum for ma
Page 235 and 236:
i j Figure 9. 1 H NMR spectrum for
Page 237 and 238:
i Figure 13. DEPT-135 spectrum for
Page 239 and 240:
Scheme 1. General mechanism of frag
Page 241 and 242:
Intens. [%] 100 80 60 40 20 0 O H N
Page 243 and 244:
Intens. [%] 100 1131.3 80 60 40 20
Page 245 and 246:
Intens. 1500 1528.6088 1000 500 150
Page 247 and 248:
Intens. [%] 100 80 60 40 Free guest
Page 249 and 250:
Intens. 4 x10 1085.3575 1.25 1.00 0
Page 251 and 252:
Intens. [%] 100 80 Free guest 586.1
Page 253 and 254:
Synthesis, self-assembly and ESI-MS
Page 255 and 256:
O O HN NH HN O O NH HN O 11 O NH O
Page 257 and 258:
O O HN NH HN O O NH HN O 9 O NH O O
Page 259 and 260:
H 2 O DMSO DMSO Figure 6. 1 H-NMR a
Page 261 and 262:
Intens. 5 x10 5 -MS 487.1588 4 3 2
Page 263 and 264:
Intens. -MS 6 x10 0.8 0.6 0.4 0.2 1
Page 265 and 266:
Intens. -MS 6 x10 O O 350.9 1.5 1.0
Page 267 and 268:
Intens. [%] 100 -MS 486.9 Exact str
Page 269 and 270:
Intens. [%] -MS 100 486.9 80 60 975
Page 271 and 272:
Intens. [%] +MS 100 80 517.2 Exact
Page 273 and 274:
Intens. [%] 100 80 60 +MS 388.1 775
Page 275 and 276:
Intens. [%] 100 +MS 517.2 Exact str
Page 277 and 278:
Intens. [%] 100 80 +MS 1031.4939 7
Page 279 and 280:
Intens. [%] 100 +MS 517.2 Exact str
Page 281 and 282:
Intens. [%] 100 -MS 2 586.1 80 60 4
Page 283 and 284:
Intens. [%] 100 -MS 2 875.2 Exact s
Page 285 and 286:
Table 1. High resolution ESI-TOF/MS
Page 287 and 288:
274 | P a g e
Page 289 and 290:
276 | P a g e
Page 291:
4. H. Nour, A. López-Periago, N. K
show all

The Development of Novel Antibiotics Using ... - Jacobs University

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?