Click Reactions in Organic Synthesis by Srinivasan Chandrasekaran (Editor)

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Click Reactions in Organic Synthesis

Srinivasan Chandrasekaran (Editor)
360 pages
June 2016

 

 

Description

This book on click reactions to focus on organic synthesis, this reference work describes the click concept and underlying mechanisms as well as the main applications in various fields. As such, the chapters cover green chemical synthesis, metal-free click reactions, synthesis of pharmaceuticals, peptides, carbohydrates, DNA, macrocycles, dendrimers, polymers, and supramolecular architectures.
By filling a gap in the market, this is the ultimate reference for synthetic chemists in academia and industry aiming for a fast and simple design and synthesis of novel compounds with useful properties.

Table of Contents

List of Contributors XI

Preface XV

1 Click Chemistry:Mechanistic and Synthetic Perspectives 1
Ramesh Ramapanicker and Poonam Chauhan

1.1 Cycloaddition Click Reactions 2

1.1.1 Azide–Alkyne Huisgen 1,3-Dipolar Cycloaddition 2

1.1.2 Copper-Catalyzed Azide–Alkyne Cycloaddition (CuAAC) Click Reaction 2

1.1.2.1 Mechanism of CuAAC Click Reactions 5

1.1.2.2 Catalysts used for CuAAC Click Reactions 6

1.1.2.3 Ligands used for CuAAC Click Reactions 7

1.1.3 Ruthenium-Catalyzed Azide–Alkyne Cycloaddition (RuAAC) Click Reactions 7

1.1.3.1 Mechanism of RuAAC Click Reactions 8

1.1.4 Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC) Reactions 8

1.1.5 Organocatalytic Triazole Formation 10

1.2 Thiol-Based Click Reactions 12

1.2.1 Radical Click Reactions of Thiols 12

1.2.1.1 Thiol–Ene Radical Click Reaction 12

1.2.1.2 Thiol–Yne Radical Click Reaction 14

1.2.2 Nucleophilic Addition Click Reactions ofThiols 15

1.2.2.1 Thiol–Epoxide Click Reactions 17

1.2.2.2 Thiol–Isocyanate Click Reactions 17

1.2.2.3 Thiol–Michael Addition Click Reactions 18

1.2.2.4 Thiol–Halogen Nucleophilic Substitution Reaction 20

1.3 Miscellaneous Click Reactions 21

References 22

2 Applications of Click Chemistry in Drug Discovery and Development 25
Balasubramanian Gopalan and Kalpattu Kuppusamy Balasubramanian

2.1 Introduction 25

2.2 Part A: Application of Click Chemistry to Drug Discovery and Development 25

2.2.1 Carbonic Anhydrase Inhibitors 30

2.2.2 Targeting Onchocerca Volvulus Chitinase-1 (OvCHT1) using the Hydroxytriazole Moiety within a Scaffold Hopping Approach 32

2.2.3 1,2,3-Triaole-Derived Anticancer Agents 34

2.2.3.1 Topoisomerase II Inhibitors 34

2.2.3.2 Histone Deacetylase Inhibitors 36

2.2.3.3 Protein Tyrosine Kinase Inhibitors 38

2.2.3.4 Antimicrotubule Agents 39

2.2.3.5 HSP 90 Inhibitors 40

2.2.3.6 Autophagy-Dependent Apoptosis in CancerTherapy 41

2.2.3.7 Anticancer Activity of 4β-Triazole-Podophyllotoxin 42

2.2.3.8 1,2,3-Triazole-Substituted Oleanolic Acid Derivatives as Anticancer Agents 42

2.2.3.9 Anti-Infective Agents 43

2.2.3.10 1,2,3-Triazole Nucleoside 44

2.2.3.11 1,2,3-Triazole Carbonucleosides 45

2.2.3.12 β-Lactamase Inhibitors as Antibacterial Agents 47

2.2.3.13 1,2,3-Triazole-Linked Carbazoles as Antitubercular Agents 48

2.2.3.14 1,4-Diaryl-Substituted 1,2,3-Traizoles as Antimycobacterial (Mtb) Agents 48

2.2.3.15 1,2,3-Triazole-Adamantylacetamide Hybrids as Antitubercular Agents 50

2.2.3.16 Non-Nucleoside HIV Integrase Inhibitors 50

2.2.3.17 MiscellaneousTherapeutic Segments: 1,2,3-Triazole-Linked Dopamine D3 Receptor (D3R) 53

2.2.3.18 Peptidomimetics: 1,2,3-Triazole as a Disulfide Bond Mimetic 53

2.3 Part B: Synthesis of Triazole-Based Drugs Currently in use 54

2.2.1 Tazobactam 54

2.3.1.1 Synthesis of tazobactam from intermediate 102 55

2.3.1.2 Other reports on Tazobactam synthesis 55

2.3.2 Solithromycin 56

2.3.2.1 Synthesis of Solithromycin 57

2.3.3 Cefatrizine 60

2.3.4 Radezolid 61

2.3.5 Molidustat 63

2.3.5.1 Synthesis of Molidustat 63

2.3.6 Tradipitant 63

2.3.7 Carboxyamidotriazole 66

2.3.8 Rufinamide 66

2.3.8.1 Rufinamide–Novartis Process 66

2.3.8.2 An Efficient Synthesis of Rufinamide 68

2.3.8.3 Continuous-Flow Total Synthesis of Rufinamide 68

References 70

3 Green Chemical Synthesis and Click Reactions 77
Maria José Arévalo, Óscar López, and Maria Victoria Gil

3.1 Introduction 77

3.2 Huisgen 1,3-Dipolar Cycloaddition 77

3.2.1 Green Perspectives on Reaction Conditions 78

3.2.1.1 Copper(I) Catalysts 78

3.2.1.2 Copper(I) Complexes with Nitrogen- and Phosphorous-Donating Ligands 79

3.2.1.3 Metalated Reagents as Catalysts 82

3.2.1.4 Immobilized Copper Species 82

3.2.1.5 Copper Nanocatalysis 83

3.2.1.6 Other Metals as Catalysts 84

3.2.1.7 Nonconventional Energy Sources 85

3.2.2 Applications to Synthesis 85

3.2.2.1 Regioselectivity of the Alkyne–Azide Cycloaddition 85

3.2.2.2 Different Substitution Patterns on Triazole 86

3.2.2.3 Strain-Promoted Cycloadditions 87

3.2.2.4 Sulfonyl Azides in Huisgen Cycloaddition 87

3.2.2.5 Synthesis of Vinyl-1,2,3-Triazoless 87

3.2.2.6 Triazole Derivative Ligands for Coordination Chemistry 88

3.2.2.7 Tetrazole Synthesis 88

3.2.2.8 Synthesis of Chiral Triazoles 88

3.2.2.9 Synthesis of Triazoles with Luminescent Properties 89

3.2.2.10 Synthesis of Triazole Libraries 89

3.2.2.11 Synthesis of Phosphorylated Triazoles 89

3.3 Other 1,3-Dipolar Cycloadditions 90

3.4 Atom Economy and Simplicity of Procedures in Multicomponent Reactions 90

3.4.1 Reaction Conditions 91

3.4.1.1 Copper Compounds as Catalysts 91

3.4.1.2 Copper Complexes with Nitrogen- and Phosphorous-Donating Ligands 91

3.4.1.3 Immobilized Copper Species 91

3.4.1.4 Copper Nanocatalysis 92

3.5 Summary and Conclusions 92

References 93

4 Synthesis of Substituted 1,2,3-Triazoles through Organocatalysis 99
Kengadarane Anebouselvy and Dhevalapally B. Ramachary

4.1 Introduction 99

4.2 Preformed-Enolate-Based Synthesis of Substituted 1,2,3-Triazoles 101

4.3 Preformed-Enamine-Based Synthesis of Substituted 1,2,3-Triazoles 106

4.4 Synthesis of Substituted 1,2,3-Triazoles via Catalytic Enolate Intermediates 109

4.5 General Mechanistic Aspects of Enolate Route 113

4.6 Synthesis of Substituted 1,2,3-Triazoles via Enamine Intermediates 114

4.7 General Mechanistic Aspects of Enamine Route 123

4.8 Synthesis of Substituted 1,2,3-Triazoles via Iminium Intermediate 123

4.9 Miscellaneous Routes for the Synthesis of 1,2,3-Triazoles 124

4.10 Conclusions 136

Acknowledgments 136

References 137

5 Applications of the Cu-Catalyzed Azide–Alkyne Cycloaddition (CuAAC) in Peptides 141
Freek A. B. M. Hoogstede and Floris P. J. T. Rutjes

5.1 Introduction 141

5.2 CuAAC-Mediated Peptide Conjugation Strategies 142

5.3 CuAAC-Mediated Peptide Backbone Modification Strategies 148

5.4 Conclusions 157

References 157

6 Synthesis of Diverse Carbohydrate-Based Molecules using Click Chemistry 161
Anoop S. Singh, Kunj B.Mishra, AmritaMishra, and Vinod K. Tiwari

6.1 Introduction 161

6.2 Cu-Catalyzed Click Chemistry in the Synthesis of Diverse Glycoconjugates 162

6.3 Synthesis of Carbohydrate-Based Simple to Complex Macrocycles 181

6.4 Click-Inspired Synthesis of Diverse Neoglycoconjugates 185

6.5 Conclusion and Future Perspective 195

Acknowledgment 196

References 196

7 Azide–Alkyne Click Reaction in Polymer Science 203
Joydeb Mandal and S. Ramakrishnan

7.1 Introduction 203

7.2 Linear, Dendritic, and Hyperbranched Polymers 205

7.3 Telechelic and Block Copolymers 220

7.4 Star and Star-Block Polymers 226

7.5 Cyclic Polymers 230

7.6 Side-Chain Clickable Polymers 235

7.7 Cross-linked Polymeric Systems 238

7.8 Porous Organic Polymers 242

7.9 Surface Modification using CuAAC Reaction 244

7.10 Strain-Promoted Click Reaction 247

7.11 Topochemical Azide–Alkyne Cycloaddition (TAAC) Reactions 249

7.12 Summary and Outlook 251

References 251

8 Thiol-Based “Click” Chemistry for Macromolecular Architecture Design 255
Weidong Zhang, Kui Chen, and Gaojian Chen

8.1 Introduction 255

8.2 Thiol Chemistry for Macromolecular Architecture Design 256

8.2.1 Linear Polymers 256

8.2.2 Graft and Comb Polymers 258

8.2.3 Star Polymers 261

8.2.4 Cyclic Polymers 263

8.2.5 Dendritic and Hyperbranched Polymers 265

8.2.6 Conjugated and Hybrid Polymers 270

8.3 Conclusion 276

Acknowledgments 284

References 284

9 Synthesis of Macrocycles and Click Chemistry 287
Dario Pasini

9.1 Introduction 287

9.1.1 Peptide- and Sugar-Containing Click Macrocycles 289

9.1.2 Click Macrocycles for Anion Binding and Supramolecular Recognition 297

9.1.3 Clicking Macrocycles to form Mechanical Bonds 300

9.1.4 Cyclic Polymers Obtained by the CuAAC Click Reaction 302

9.2 Summary and Conclusions 304

References 304

10 Modifications of Nucleosides, Nucleotides, and Nucleic Acids using Huisgen’s [3+2] Azide–Alkyne Cycloaddition: Opening Pandora’s Box 309
Franck Amblard, Ozkan Sari, Sebastien Boucle, Ahmed Khalil, and Raymond F. Schinazi

10.1 Introduction 309

10.1.1 Nucleoside Modifications 309

10.1.1.1 Nucleoside Analogs as Potential Drugs 309

10.1.1.2 Nucleoside Bioconjugates 311

10.2 Nucleotide and Nucleic Acid Modifications 316

10.2.1 “Artificial” DNA 316

10.2.2 Presynthetic Modification DNA 316

10.2.3 Postsynthetic Modification 318

10.3 Conclusion 331

Acknowledgments 332

References 332

Index 337

Author Information

Srinivasan Chandrasekaran is an Honorary Professor and SERB Distinguished Fellow at the Department of Organic Chemistry, Indian Institute of Science, Bangalore, India. He received his M.Sc. and Ph.D. from the University of Madras, India, in 1967 and 1972, respectively. He was a research associate at Harvard University (USA) with Prof. E.J. Corey, and Syntex Research (Palo Alto, USA). He has published over 250 research papers in national and international journals and served as an elected member of the Bureau of IUPAC and Member of the Executive Committee of IUPAC. He is the Chairman of the National Organic Symposium Trust (NOST), India and was the President of the Chemical Research Society of India (CRSI) from 2012 to 2014. He was the editor-in-chief of Tetrahedron Letters published by Elsevier( 2007-14) and is currently on the Board of Consulting Editors. His major research interests lie in the areas of development of new synthetic methodologies and organometallic chemistry, total synthesis of natural products, homogeneous and heterogeneous catalysis, and organic materials.

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