Presents a comprehensive account of established protecting-group-free synthetic routes to molecules of medium to high complexity
This book supports synthetic chemists in the design of strategies, which avoid or minimize the use of protecting groups so as to come closer to achieving an “ideal synthesis” and back the global need of practicing green chemistry. The only resource of its kind to focus entirely on protecting-group-free synthesis, it is edited by a leading practitioner in the field, and features enlightening contributions by top experts and researchers from across the globe.
The introductory chapter includes a concise review of historical developments, and discusses the concepts, need for, and future prospects of protecting-group-free synthesis. Following this, the book presents information on protecting-group-free synthesis of complex natural products and analogues, heterocycles, drugs, and related pharmaceuticals. Later chapters discuss practicing protecting-group-free synthesis using carbohydrates and of glycosyl derivatives, glycol-polymers and glyco-conjugates. The book concludes with a chapter on latent functionality as a tactic toward formal protecting-group-free synthesis.
- A comprehensive account of established protecting-group-free (PGF) synthetic routes to molecules of medium to high complexity
- Benefits total synthesis, methodology development and drug synthesis researchers
- Supports synthetic chemists in the design of strategies, which avoid or minimize the use of protecting groups so as to come closer to achieving an “ideal synthesis” and support the global need of practicing green chemistry
- Covers a topic that is gaining importance because it renders syntheses more economical
Protecting-Group-Free Organic Synthesis: Improving Economy and Efficiency is an important book for academic researchers in synthetic organic chemistry, green chemistry, medicinal and pharmaceutical chemistry, biochemistry, and drug discovery.
Table of Contents
List of Contributors xi
Foreword by Prof. W. Hoffmann xiii
Foreword by Prof. G. Mehta xv
Preface xvii
1 Introduction: Concepts, History, Need, and Future Prospects of Protecting-Group-Free Synthesis 1
Rodney A. Fernandes
1.1 Introduction, Concepts, and Brief History 1
1.2 Need and Future Prospects of Protecting-Group-Free Synthesis 7
References 8
2 Protecting-Group-Free Synthesis of Natural Products and Analogs, Part I 11
Rodney A. Fernandes
2.1 Introduction 11
2.2 Mytilipin A 12
2.3 Chokols 13
2.4 (±)-Diospongin A 14
2.5 (−)-Bitungolide F 15
2.6 (+)-Brevisamide 16
2.7 21,22-Diepi-membrarolin 17
2.8 (±)-Pogostol and (±)-Kessane 18
2.9 (+)-Allopumiliotoxin 267A 19
2.10 (−)-Hortonones A-C 19
2.11 (−)-Heliophenanthrone 21
2.12 (−)-Pycnanthuquinone C 21
2.13 (+)-Aplykurodinone-1 22
2.14 (±)-Hippolachnin A 23
2.15 (+)-Linoxepin 25
2.16 (+)-Antofine and (-)-Cryptopleurine 26
2.17 (+)-Tylophorine 28
2.18 (±)-Cruciferane 30
2.19 (+)-Artemisinin 31
2.20 (±)-Dievodiamine 32
2.21 (−)-Chaetominine 33
2.22 Rubicordifolin 34
2.23 (+)-Caribenol A 35
2.24 Camptothecin and 10-Hydroxycamptothecin 35
2.25 (+)-Ainsliadimer A 37
2.26 Cannabicyclol, Clusiacyclols A and B, Iso-Eriobrucinols A and B, and Eriobrucinol 37
2.27 (−)-Mersicarpine, (−)-Scholarisine G, (+)-Melodinine, (−)-Leuconoxine, and (−)-Leuconolam 38
2.28 (−)-Lannotinidine B 40
2.29 (−)-Lycopodine 41
2.30 (−)-Lycospidine A 42
2.31 Transtaganolides C and D 43
2.32 (+)-Chatancin 44
2.33 (−)-Jiadifenolide 45
2.34 Pallambins C and D 46
2.35 (+)-Vellosimine 46
2.36 (−)-Pallavicinin and (+)-Neopallavicinin 47
2.37 Asteriscunolides A-D and Asteriscanolide 49
2.38 (−)-and (+)-Palmyrolide A 50
2.39 (±)-Bipinnatin J 51
2.40 Cyanolide 52
2.41 Conclusions 53
References 55
3 Protecting-Group-Free Synthesis of Natural Products and Analogs, Part II 59
Hiroyoshi Takamura and Isao Kadota
3.1 Introduction 59
3.2 Hapalindole U and Ambiguine H 60
3.3 Stenine 61
3.4 Neostenine 63
3.5 Englerin A 64
3.6 Shimalactones A and B 66
3.7 Cyanthiwigin F 66
3.8 Sintokamides A, B, and E 69
3.9 Ecklonialactones A and B 69
3.10 (E)- and (Z)-Alstoscholarines 72
3.11 Berkelic Acid 73
3.12 Myxalamide A 74
3.13 Pipercyclobutanamide A 76
3.14 Fusarisetin A 78
3.15 Rhazinilam 78
3.16 Yezo'otogirin C 81
3.17 Clavosolide A 81
3.18 Conclusion 84
References 84
4 Protecting-Group-Free Synthesis of Natural Products and Analogs, Part III 87
Alakesh Bisai and Vishnumaya Bisai
4.1 Introduction 87
4.2 Syntheses of Naturally Occurring Alkaloids 88
4.3 Syntheses of Naturally Occurring Terpenoids 105
4.4 Conclusions 124
References 125
5 Protecting-Group-Free Synthesis of Heterocycles 133
Trapti Aggarwal and Akhilesh K. Verma
5.1 Introduction 133
5.2 Historical Background of Protection-Free Strategy 134
5.3 Protecting-Group-Free (PGF) Strategy for the Synthesis of N-Heterocycles 135
5.3.1 Carbazole Substituted Compounds Using PGF Strategy 135
5.3.2 Protection-Free Synthesis of Indole-Substituted Compounds 139
5.3.3 Synthesis of Pyrrole Analogs Using Protecting-Group-Free Strategy 140
5.4 Protection-Free Synthesis of Quinoline Derivatives 142
5.5 Synthesis of Piperidine-Containing Heterocycles Without Using Protecting Groups 143
5.6 Synthesis of Quinazolines Without Using Protecting Groups 144
5.7 Protection-Free Synthesis of Pyrrolizine Alkaloid (−)-Rosmarinecine 145
5.8 Protecting-Group-Free Synthesis of O-Heterocycles 145
5.9 Protecting-Group-Free Synthesis of N,S-Heterocycles 148
5.10 Protection-Free Synthesis of Macrocyclic Ring Heterocycles 149
5.11 Protection-Free Synthesis of Thiophene Polymer 150
5.12 Protection-Free Synthesis of Azaborine 150
5.13 Conclusion 151
References 151
6 Protecting-Group-Free Synthesis of Drugs and Pharmaceuticals 155
Remya Ramesh, Swapnil Sonawane, D. Srinivasa Reddy, and Rakeshwar Bandichhor
6.1 Introduction 155
6.2 Raltegravir 158
6.3 Levetiracetam 160
6.4 Sitagliptin 163
6.4.1 Medicinal Chemistry Route 164
6.4.2 Process Chemistry Route 166
6.4.3 Greener Approach 167
6.5 Paroxetine 168
6.5.1 Medicinal Chemistry Route 168
6.5.2 Process Chemistry Route 170
6.5.3 Greener Approach 170
6.6 Synthesis
of PI3K/mTOR Inhibitor Apitolisib 171
6.7 Azepinomycin 174
6.8 One-Pot Synthesis of Sulfanyl-histidine 175
6.9 Synthesis of an Antiwrinkle Venom Analog 175
6.10 Preparation of 5-Arylidene Rhodanine and 2,4-Thiazolidinediones 176
6.11 Se-Adenosyl-L-Selenomethionine and Analogs 177
6.12 Conclusions 178
Acknowledgment 179
References 179
7 Protecting-Group-Free Synthesis in Carbohydrate Chemistry 183
Alejandro Cordero-Vargas and Fernando Sartillo-Piscil
7.1 Introduction 183
7.2 Protecting-Group-Free Total Synthesis (PGF-TS) 184
7.3 Selective PGF Functionalization at the Anomeric Position (O-, N-, and C-Glycosylation) 189
7.4 Selective PGF Functionalization at the Anomeric and Nonanomeric Positions (Oxidations) 196
7.5 Conclusion 197
References 198
8 Protecting-Group-Free Synthesis of Glycosyl Derivatives, Glycopolymers, and Glycoconjugates 201
Tomonari Tanaka
8.1 Introduction 201
8.2 Protecting-Group-Free Synthesis of Glycosyl Derivatives from Free Saccharides 202
8.3 Protecting-Group-Free Synthesis of Glycopolymers 214
8.4 Protecting-Group-Free Synthesis of Glycoconjugates 219
8.5 Conclusions 223
References 225
9 Latent Functionality: A Tactic Toward Formal Protecting-Group-Free Synthesis 229
Rodney A. Fernandes
9.1 Introduction 229
9.2 Latent Functionality for Direct Conversions Using Short-Term Latent Groups 230
9.3 Silicon-Centered Latent Functionalities 235
9.4 Latent Functionality in Total Synthesis (Long-Term Latent Groups) 240
9.5 Symmetry-Based Latent Functionality Considerations 248
9.6 Conclusions 254
References 255
Index 259
