Foreword XVII Preface XIX Acknowledgement XXIII Abbreviations XXV 1 The Concept of Synthesis 1 1.1 Organic Synthesis as a Central Science 1 1.2 Organic Chemistry and the Public 3 1.3 The "Small Molecules" of life 6 1.4 Nature's Rules 9 1.5 Organic Synthesis as a Mental and Visual Science 11 1.6 Art, Architecture, and Synthesis 12 1.7 Simplification of Complexity 13 1.8 Seeing Through the Mind's Eye 15 1.9 Beauty is in the Eye of the Beholder 18 References 19 2 The "Why" of Synthesis 25 2.1 Nature the Provider, Healer, and Enticer 25 2.2 The Supply Problem 26 2.3 From Bench to Market 28 2.4 Thank you Nature! 30 2.5 Chasing Bugs with a Purpose 32 2.6 Structure-based Organic Synthesis 33 2.7 Almost There ... or Just Arrived 34 2.8 The Futility of it All 35 2.9 Synthesis as a Seeker of the Truth 36 2.10 Nature as the Ultimate Synthesizer 42 2.11 A Brave New Chemical World 43 2.11.1 Beyond the molecule 43 2.11.2 Buckyballs and fullerenes 45 2.11.3 Dendrimers 45 2.11.4 Nanochemistry 45 2.11.5 Molecular machines 46 2.12 Exploring New Synthetic Methods 47 2.12.1 The Diels-Alder reaction 48 2.12.2 The direct aldol reaction 54 2.12.3 High impact catalytic oxidation and reduction reactions 57 2.12.4 High impact catalytic olefin-producing reactions 59 References 62 3 The "What" of Synthesis 73 3.1 Periods, Trends, and Incentives 73 3.2 A Century of Synthesis 74 3.3 We the "Synthesis People" 81 3.4 Complex and Therapeutic too! 82 3.5 Peptidomimetics and Unnatural Compounds 84 3.6 Diversity Through Complexity 89 References 90 4 The "How" of Synthesis 97 4.1 The Visual Dialogue 97 4.2 The Psychobiology of Synthesis Planning 98 4.2.1 "Psychosynthesis" 101 4.3 The Agony and Ecstasy of Synthesis 102 4.4 Rembrandt Meets Woodward 104 4.4.1 Cortisone 104 4.4.2 Strychnine 108 4.4.2.1 The Woodward Synthesis 109 4.4.2.2 The Overman synthesis 111 4.4.2.3 The Kuehne synthesis 113 4.4.2.4 The Bonjoch and Bosch synthesis 114 4.4.2.5 The Shibasaki synthesis 116 4.4.2.6 The Fukuyama synthesis 118 4.4.2.7 The Mori synthesis 119 4.4.2.8 The MacMillan synthesis 121 4.4.2.9 Strychnine syntheses: Synopsis 122 4.5 The Post Woodwardian Era 123 4.5.1 The convergent template-based approach 123 4.5.2 Chiral auxiliary approach 125 4.5.3 Substrate control approach in cycloadditions 127 4.5.4 Biomimetic cyclization approach 129 4.6 Catalysis and Chirality in Total Synthesis 131 4.6.1 Applications of asymmetric catalysis to drug discovery 136 References 139 5 Sources of Enantiopure Compounds 145 5.1 Optical Resolution 146 5.2 Chemical Kinetic Resolution (KR) 147 5.2.1 Classical, natural, and parallel methods 147 5.2.2 Dynamic chemical kinetic resolution 147 5.3 Cell-free Enzyme-mediated Enantiopure Compounds 149 5.3.1 Hydrolases and ester formation 149 5.3.2 Nitrilases, amidases, and acylases 152 5.4 Cell-free Chemoenzymatic Methods 154 5.5 Metal-catalyzed Dynamic Kinetic Resolution (DKR) 154 5.6 Biocatalytic Methods for Enantiopure Compounds 155 5.6.1 Enzymatic reduction of ketones 155 5.6.2 Enzymatic hydroxylation and epoxidation 156 5.6.3 Enzymatic oxidation of alcohols 157 5.6.4 Enzymatic Baeyer-Villiger oxidation 157 5.7 Applications of Enzymatic and Chemoenzymatic Methods 158 5.8 Chemical Asymmetric Synthesis of Enantiopure Compounds 160 5.9 Enantiopure Compounds from Nature 164 References 165 6 The Chiron Approach 171 6.1 Living Through a Total Synthesis 171 6.2 Principles of the Chiron Approach 172 6.2.1 Definition 173 6.2.2 The Chiron Approach 175 6.2.3 Two philosophies, one goal 176 6.2.4 There is more than meets the eye 180 6.2.5 The flipside of molecules 183 6.2.6 Common root, different MO: chirons and synthons 184 6.2.7 To chiron or not to chiron 186 6.3 Anatomy of a Synthesis 186 References 189 7 Nature's Chirons 193 7.1 alpha-Amino Acids 193 7.2 Carbohydrates 195 7.3 alpha-Hydroxy Acids 200 7.4 Terpenes 203 7.5 Cyclitols 206 Refer