Efficiency in Natural Product Total Synthesis

Uniting the key organic topics of total synthesis and efficient synthetic methodologies, this book clearly overviews synthetic strategies and tactics applied in total synthesis, demonstrating how the total synthesis of natural products enables scientific and drug discovery. Focuses on efficiency, a fundamental and important issue in natural products synthesis that makes natural product synthesis a powerful tool in biological and pharmaceutical science Describes new methods like organocatalysis, multicomponent and cascade reactions, and biomimetic synthesis Appeals to graduate students with two sections at the end of each chapter illustrating key reactions, strategies, tactics, and concepts; and good but unfinished total synthesis (synthesis of core structure) before the last section Compiles examples of solid phase synthesis and continuing flow chemistry-based total synthesis which are very relevant and attractive to industry R&D professionals

Autorentext

Pei-Qiang Huang, PhD, is Professor of Chemistry and former Dean of the College of Chemistry and Chemical Engineering at Xiamen University. Zhu-Jun Yao, PhD, is Cyrus Tang Chair Professor and University Distinguished Professor at Nanjing University. Richard P. Hsung, PhD, is Kremers Chair and Vials Distinguished Professor of Pharmaceutical Sciences at School of Pharmacy, University of WisconsinMadison.

Klappentext
Total synthesis of natural products is one of organic chemistry's oldest disciplines, enabling chemists to duplicate nature and providing the means to examine natural phenomena more closely. The development of drugs, the examination of biopathways and many other achievements would not have been possible without total synthesis for example, about half of the drugs currently in clinical use have their origins in natural products. New concepts, strategies, and tactics for efficient total synthesis of natural products will continue as a major pursuit for synthetic organic, medicinal, and process chemists for a long time to come. Uniting the key organic topics of total synthesis and efficient synthetic methodologies, Efficiency in Natural Product Total Synthesis clearly overviews the strategies and tactics applied in total synthesis, demonstrating how the total synthesis of natural products enables scientific and drug discovery. The state-of-the-art topics covered include: economical and protecting-group-free synthesis, computer-aided total synthesis, catalytic asymmetric synthesis, biomimetic and bio-inspired synthesis, as well as different classes of organic reactions. Other chapters address chemical building blocks, technologies of chemical and biological space, and synthetic biology. A key part of the coverage is the illustration of how these practices and strategies influence drug discovery and chemical biology. Chemical researchers working with natural products synthesis will find this book to be an important reference and resource that offers a number of valuable features:

• Focus on efficiency, a fundamental and important issue in natural products synthesis that makes natural product synthesis a powerful tool in biological and pharmaceutical science
• Discussion of new methods like organocatalysis, multicomponent and cascade reactions, and biomimetic synthesis
• Sections at the end of each chapter illustrating key reactions, strategies, tactics, and concepts; and good but unfinished total synthesis (synthesis of core structure) before the last section
• Examples of solid phase synthesis and continuing flow chemistry-based total synthesis, which are very relevant for industrial R&D

Inhalt
Contributors xiii

Foreword xv

Preface xvii

**Introduction 1
**PeiQiang Huang

1 The Golden Age of the Total Synthesis of Natural Products: The Era as a Dominant Field 2

2 19912000: A Contrasting Decade 9

3 Total Synthesis in the TwentyFirst Century 10

4 The Challenges of the Efficiency in the Total Synthesis of Natural Products 12

5 The Renaissance of Natural Products as Drug Candidates 14

6 Recent Recognition of the Contribution of Natural ProductBased Drugs to Society 16

Acknowledgements 18

References 18

**1 Principles for Synthetic Efficiency and Expansion of the Field 27
**PeiQiang Huang

1.1 Concepts for Efficiency in the Total Synthesis of Natural Products 27

1.1.1 Ideal Synthesis 28

1.1.2 Selectivity 29

1.1.3 Green Synthesis 32

1.1.4 Atom Economy 32

1.1.5 E Factors 32

1.1.6 Step Economy 33

1.1.7 Pot Economy and PASE (Pot, Atom, and Step Economy) 34

1.1.8 Redox Economy 34

1.1.9 ProtectingGroupFree Synthesis 36

1.1.10 Multicomponent Reactions and OnePot Reactions 38

1.1.11 Scalability 40

1.1.12 Convergent Synthesis 41

1.2 Biomimetic Synthesis 41

1.2.1 Basic Logic of Biosynthesis 42

1.2.2 Tandem, Cascade, and Domino Reactions OnePot Reactions 42

1.2.3 Site and Stereoselective Reactions 46

1.2.4 The CH Bond Functionalization Strategy 46

1.2.5 The BuildingBlock Strategy 47

1.2.6 The Collective Synthesis Strategy 49

1.2.7 The Oligomerization Tactic 50

1.3 The Expansion of the Field: Chemical Biology/Chemical Genetics 51

1.3.1 DiversityOriented Synthesis (DOS) 51

1.3.2 FunctionOriented Synthesis (FOS) 51

1.3.3 BiologyOriented Synthesis (BIOS) 52

1.3.4 LeadOriented Synthesis (LOS) 52

1.4 Addressing the Threats that Humans May Face in the Near Future 53

1.4.1 A. G. Myers' Endeavor 53

1.4.2 D. L. Boger's Endeavor 55

Acknowledgements 56

References 56

**2 Selected ProcedureEconomical Enantioselective Total Syntheses of Natural Products 67
**PeiQiang Huang

2.1 OneStep/OnePot Enantioselective Total Synthesis of Natural Products/Drugs 68

2.1.1 Robinson's OneStep Synthesis of Tropinone 68

2.1.2 Hayashi's OnePot Synthesis of (+)ABT341 69

2.2 TwoStep/TwoPot Enantioselective Total Synthesis of Natural Products 69

2.2.1 Hayashi's TwoPot Synthesis of ()Oseltamivir 69

2.2.2 Ma's TwoPot Synthesis of ()Oseltamivir 70

2.2.3 Li's TwoStep Chemoenzymatic Total Synthesis of Aszonalenin 71

2.2.4 Ishikawa's TwoStep Total Syntheses of (+)WIN 64821 and (+)Naseseazine B 71

2.3 ThreeStep/ThreePot Enantioselective Total Synthesis of Natural Products 73

2.3.1 Carreira's ThreeStep Asymmetric Total Syntheses of (+)Aszonalenin and ()Brevicompanine B 73

2.3.2 Husson's ThreeStep Asymmetric Total Synthesis of ()Sibirine 73

2.3.3 MacMillan's ThreeStep Asymmetric Total Synthesis of (+)Frondosin B 75

2.3.4 Hayashi's ThreePot Total Synthesis of ()PGE1 Methyl Ester 75

2.3.5 Porco's ThreePot Total Synthesis of ()Hyperibone K 76

2.4 FourStep Enantioselective Total Synthesis of Natural Products 77

2.4.1 Lawrence's FourStep Total Synthesis of ()Angiopterlactone A 77

2.4.2 Maimone's FourStep Synthesis of (+)Cardamom Peroxide 78

2.4.3 Xie, Lai, and Ma's FourStep Total Synthesis of ()Chimonanthine 79

2.4.4 Huang's FourStep Total Synthesis of ()Chaetominine 80

2.5 FiveStep/Pot Enantioselective Total Synthesis of Natural Products 81

2.5.1 Carreira's FiveStep Total Syntheses of 9Tetrahydrocannabinols 81

2.5.2 Studer's FiveStep Total Syntheses of (+)Machaeriols B and D 83

2.5.3 Cook's FivePot Total Synthesis of (+)Artemisinin (Qinghaosu) 84 2.5.4 Corey's FiveStep Total Synthe...