Part One, Concepts and Strategies, discusses the linker groups used to attach the synthesis substrate to the solid support, colorimetric tests to
Table of Contents
Preface xv
Acknowledgments xvii
Contributors xix
Part I Concepts and Strategies 1
1 Linker Strategies in Modern Solid-Phase Organic Synthesis 3
Peter J. H. Scott
1.1 Introduction 3
1.2 Classical Linker Strategies 5
1.3 Multifunctional Linker Strategies 28
1.4 Conclusions 73
References 73
2 Colorimetric Test For Solid-Phase Organic Synthesis 83
Yan Teng and Patrick H. Toy
2.1 Introduction 83
2.2 Functional Group Tests 84
2.3 Conclusions 92
References 92
3 Practical Aspects of Combinatorial Solid-Phase Synthesis 95
Jan Hlavac, Miroslav Soural, and Viktor Krchnak
3.1 Introduction 95
3.2 Strategies in Combinatorial Solid-Phase Synthesis 101
3.3 Equipment and Instrumentation 112
3.4 Characterization and Purification 118
3.5 Conclusions 121
Acknowledgments 121
References 121
4 Diversity-Oriented Synthesis 131
Kieron M. G. O’Connell, Warren R. J. D Galloway, Brett M. Ibbeson, Albert Isidro-Llobet, Cornelius J. O’Connor, and David R. Spring
4.1 Introduction 131
4.2 Small Molecules and Biology 131
4.3 Diversity-Oriented Synthesis, Target-Oriented Synthesis, and Combinatorial Chemistry 133
4.4 Molecular Diversity 134
4.5 Diversity-Oriented Synthesis on Solid Phase 137
4.6 Diversity-Oriented Synthesis Around Privileged Scaffolds 146
4.7 Diversity Linker Units in Solid-Phase Organic Synthesis 147
4.8 Conclusions 148
References 149
5 Diversity-Oriented Synthesis of Privileged Heterocycles Using Divergent Strategy 151
Seung Bum Park and Jonghoon Kim
5.1 Introduction 151
5.2 Divergent Synthesis of Natural Product-Like Polyheterocycles Using a Cyclic Iminium as a Single Key Intermediate 153
5.3 Conclusions 168
References 168
6 Chemo- and Regioselectivity Enhancement in Solid-Supported Reactions 171
Douglas D. Young and Alexander Deiters
6.1 Introduction 171
6.2 Transition Metal-Mediated Solid-Supported Reactions 172
6.3 Non-transition Metal-Mediated Solid-Supported Reactions 186
6.4 Traceless Cleavage 192
6.5 Conclusions 201
References 201
Part II Applications 205
7 Asymmetric Synthesis On Solid Support 207
Baburaj Baskar and Kamal Kumar
7.1 Introduction 207
7.2 Asymmetric Chemical Transformations of Solid-Supported Substrates 208
7.3 Asymmetric Transformations Using Resin-Bound Chiral Catalysts and Auxiliaries 219
7.4 Conclusions 227
References 227
8 Recent Advances in Microwave-Assisted Solid-Phase Synthesis of Heterocycles 231
Prasad Appukkuttan, Vaibhav, P. Mehta, and Erik Van der Eycken
8.1 Introduction 231
8.2 Fused 1,3-oxazin-6-ones 232
8.3 Thiazolo[4,5-d]pyrimidine-5,7-diones 233
8.4 Pyrazoles 234
8.5 HSP70 Modulators 234
8.6 Benzimidazo[2,1-b]quinazolin-12(5H)-ones 236
8.7 Imidazoles 237
8.8 1,4-Naphthoquinones 238
8.9 Phthalocyanines 238
8.10 1,2,3,4-Tetrahydroquinolines 242
8.11 1,2,3-Triazoles 243
8.12 2,8-Diaminopurines 244
8.13 Imidazolidin-4-ones 245
8.14 Indoles 247
8.15 1,2,3,4-Tetrahydroquinolines Using a SmI2-Cleavable Linker 248
8.16 Hydantoins 249
8.17 Imatinib 250
8.18 Isoindolines 252
8.19 2-(Benzylthio)imidazo[1,2a]-pyrimidin-5-ones 253
8.20 2-Aminobenzothiazoles 254
8.21 Pyrimidines, Pyrazoles, and Isoxazoles 255
8.22 Quinolin-2(1H)-ones and Coumarins 256
8.23 Benzofurans 257
8.24 i-Condensed Purines 258
8.25 2(1H)-Pyrazinones 259
8.26 Conclusions 260
References 261
9 Solid-Phase Synthesis of Heterocycles From Peptides and Amino Acids 269
Zhi Li, Marc Giulianotti, Wenteng Chen, Richard A. Houghten, and Yongping Yu
9.1 Introduction 269
9.2 Synthesis of Various Heterocycles 269
References 316
10 Generation of Drug-Like Five-Membered Heterocyclic Libraries Using Carbon Disulfide and Merrifield Resin 319
Young-Dae Gong and Taeho Lee
10.1 Introduction 319
10.2 Solid-Phase Synthesis of Related Thiazole Compounds 320
10.3 Solid-Phase Synthesis of Benzoxazoles 333
10.4 Solid-Phase Synthesis of Related Pyrazole Compounds and 1,3,4-Triazoles via a Dithiocarbazate Linker 334
10.5 Solid-Phase Synthesis of 1,3,4-Oxadiazoles and 1,3,4-Thiadiazoles via Selective Cyclization 342
10.6 Solid-Phase Synthesis of 1,2,4-Thiadiazoles 347
10.7 Summary 350
References 350
11 Recent Advances in Solid-Phase 1,3-Dipolar Cycloaddition Reactions 355
Kirsi Harju and Jari Yli-Kauhaluoma
11.1 Introduction 355
11.2 Solid-Phase Synthesis of Pyrrolidines, Pyrrolines, and Pyrroles 356
11.3 Synthesis of Pyrazolines and Pyrazoles 361
11.4 Solid-Phase Synthesis of Imidazoles, 1,2,4-Triazoles, and 1,2,3-Triazoles 364
11.5 Solid-Phase Synthesis of Isoxazolidines, Isoxazolines, and Isoxazoles 369
11.6 Conclusions 378
References 378
12 Sulfones in Solid-Phase Heterocycle Synthesis 383
Chai Hoon Soh and Yulin Lam
12.1 Introduction 383
12.2 Linkers 384
12.3 Conclusions 411
References 411
13 Solid-Phase Organic Radiosynthesis 415
Raphael Hoareau and Peter J. H. Scott
13.1 Introduction 415
13.2 Solid-Phase Organic Radiosynthesis with Fluorine-18 416
13.3 Solid-Phase Organic Radiosynthesis with Carbon-11 421
13.4 Solid-Phase Organic Radiosynthesis with Other Radioisotopes 422
13.5 Conclusions 424
References 424
14 Solid-Phase Synthesis of Dyes and Their Application As Sensors and Bioimaging Probes 427
Marc Vendrell, Hyung-Ho Ha, Sung Chan Lee, and Young-Tae Chang
14.1 Introduction 427
14.2 On-Bead Sensors 428
14.3 Solid-Phase Approaches in Fluorescent Labeling 429
14.4 Solid-Phase Derivatization of Fluorescent Scaffolds 430
14.5 Diversity-Oriented Fluorescent Libraries 433
14.6 Conclusions 437
14.7 Acknowledgments 437
References 437
15 Dendritic Molecules On Solid Support: Solid-Phase Synthesis and Applications 441
Kerem Goren and Moshe Portnoy
15.1 Introduction 441
15.2 Synthesis 442
15.3 Applications of Dendronized Supports 464
15.4 Conclusions 480
References 482
16 Oligosaccharide Synthesis On Solid, Soluble Polymer, and Tag Supports 489
Katsunori Tanaka and Koichi Fukase
16.1 Introduction 489
16.2 Solid-Phase Methods for Synthesis of Oligosaccharides 490
16.3 Polymer-Supported and Tag-Assisted Oligosaccharide Synthesis in Solution 516
16.4 Conclusions 526
16.5 Acknowledgments 527
References 527
Index 531
