Alexandros L. Zografos,
AL Zografos
John Wiley & Sons
e druk, 2016
9781118751732
From Biosynthesis to Total Synthesis – Strategies and Tactics for Natural Products
Strategies and Tactics for Natural Products
Specificaties
Gebonden, 584 blz.
|
Engels
John Wiley & Sons |
e druk, 2016
ISBN13: 9781118751732
Rubricering
Verwachte levertijd ongeveer 16 werkdagen
Samenvatting
Focusing on biosynthesis, this book provides readers with approaches and methodologies for modern organic synthesis. By discussing major biosynthetic pathways and their chemical reactions, transformations, and natural products applications; it links biosynthetic mechanisms and more efficient total synthesis.
Describes four major biosynthetic pathways (acetate, mevalonate, shikimic acid, and mixed pathways and alkaloids) and their related mechanisms
Covers reactions, tactics, and strategies for chemical transformations, linking biosynthetic processes and total synthesis
Includes strategies for optimal synthetic plans and introduces a modern molecular approach to natural product synthesis and applications
Acts as a key reference for industry and academic readers looking to advance knowledge in classical total synthesis, organic synthesis, and future directions in the field
Specificaties
Inhoudsopgave
<p>LIST OF CONTRIBUTORS xiii</p>
<p>PREFACE xv</p>
<p>1 From Biosyntheses to Total Syntheses: An Introduction 1<br /> Bastien Nay and Xu Wen Li</p>
<p>1.1 From Primary to Secondary Metabolism: the Key Building Blocks 1</p>
<p>1.1.1 Definitions 1</p>
<p>1.1.2 Energy Supply and Carbon Storing at the Early Stage of Metabolisms 1</p>
<p>1.1.3 Glucose as a Starting Material Toward Key Building Blocks of the Secondary Metabolism 1</p>
<p>1.1.4 Reactions Involved in the Construction of Secondary Metabolites 3</p>
<p>1.1.5 Secondary Metabolisms 4</p>
<p>1.2 From Biosynthesis to Total Synthesis: Strategies Toward the Natural Product Chemical Space 10</p>
<p>1.2.1 The Chemical Space of Natural Products 10</p>
<p>1.2.2 The Biosynthetic Pathways as an Inspiration for Synthetic Challenges 11</p>
<p>1.2.3 The Science of Total Synthesis 14</p>
<p>1.2.4 Conclusion: a Journey in the Future of Total Synthesis 16</p>
<p>References 16</p>
<p>SECTION I ACETATE BIOSYNTHETIC PATHWAY 19</p>
<p>2 Polyketides 21<br /> Françoise Schaefers, Tobias A. M. Gulder, Cyril Bressy, Michael Smietana, Erica Benedetti, Stellios Arseniyadis, Markus Kalesse, and Martin Cordes</p>
<p>2.1 Polyketide Biosynthesis 21</p>
<p>2.1.1 Introduction 21</p>
<p>2.1.2 Assembly of Acetate/Malonate Derived Metabolites 23</p>
<p>2.1.3 Classification of Polyketide Biosynthetic Machineries 23</p>
<p>2.1.4 Conclusion 39</p>
<p>References 40</p>
<p>2.2 Synthesis of Polyketides 44</p>
<p>2.2.1 Asymmetric Alkylation Reactions 44</p>
<p>2.2.2 Applications of Asymmetric Alkylation Reactions in Total Synthesis of Polyketides and Macrolides 60</p>
<p>References 83</p>
<p>2.3 Synthesis of Polyketides Focus on Macrolides 87</p>
<p>2.3.1 Introduction 87</p>
<p>2.3.2 Stereoselective Synthesis of 1,3 Diols: Asymmetric Aldol Reactions 88</p>
<p>2.3.3 Stereoselective Synthesis of 1,3 Diols: Asymmetric Reductions 106</p>
<p>2.3.4 Application of Stereoselective Synthesis of 1,3 Diols in the Total Synthesis of Macrolides 117</p>
<p>2.3.5 Conclusion 126</p>
<p>References 126</p>
<p>3 Fatty Acids and their Derivatives 130<br /> Anders Vik and Trond Vidar Hansen</p>
<p>3.1 Introduction 130</p>
<p>3.2 Biosynthesis 130</p>
<p>3.2.1 Fatty Acids and Lipids 130</p>
<p>3.2.2 Polyunsaturated Fatty Acids 134</p>
<p>3.2.3 Mediated Oxidations of 3 and 6 Polyunsaturated Fatty Acids 135</p>
<p>3.3 Synthesis of 3 and 6 All Z Polyunsaturated Fatty Acids 140</p>
<p>3.3.1 Synthesis of Polyunsaturated Fatty Acids by the Wittig Reaction or by the Polyyne Semihydrogenation 140</p>
<p>3.3.2 Synthesis of Polyunsaturated Fatty Acids via Cross Coupling Reactions 143</p>
<p>3.4 A pplications in Total Synthesis of Polyunsaturated Fatty Acids 145</p>
<p>3.4.1 Palladium Catalyzed Cross Coupling Reactions 145</p>
<p>3.4.2 Biomimetic Transformations of Polyunsaturated Fatty Acids 149</p>
<p>3.4.3 Landmark Total Syntheses 153</p>
<p>3.4.4 Synthesis of Leukotriene B5 158</p>
<p>3.5 Conclusion 160</p>
<p>Acknowledgments 160</p>
<p>References 160</p>
<p>4 Polyethers 162<br /> Youwei Xie and Paul E. Floreancig</p>
<p>4.1 Introduction 162</p>
<p>4.2 Biosynthesis 162</p>
<p>4.2.1 Ionophore Antibiotics 162</p>
<p>4.2.2 Marine Ladder Toxins 165</p>
<p>4.2.3 A nnonaceous Acetogenins and Terpene Polyethers 165</p>
<p>4.3 Epoxide Reactivity and Stereoselective Synthesis 166</p>
<p>4.3.1 Regiocontrol in Epoxide Opening Reactions 166</p>
<p>4.3.2 Stereoselective Epoxide Synthesis 172</p>
<p>4.4 A pplications to Total Synthesis 176</p>
<p>4.4.1 Acid Mediated Transformations 176</p>
<p>4.4.2 Cascades via Epoxonium Ion Formation 179</p>
<p>4.4.3 Cyclizations under Basic Conditions 181</p>
<p>4.4.4 Cyclization in Water 182</p>
<p>4.5 Conclusions 183</p>
<p>References 184</p>
<p>SECTION II MEVALONATE BIOSYNTHETIC PATHWAY 187</p>
<p>5 From Acetate to Mevalonate and Deoxyxylulose Phosphate Biosynthetic Pathways: an Introduction to Terpenoids 189<br /> Alexandros L. Zografos and Elissavet E. Anagnostaki</p>
<p>5.1 Introduction 189</p>
<p>5.2 Mevalonic Acid Pathway 191</p>
<p>5.3 Mevalonate Independent Pathway 192</p>
<p>5.4 Conclusion 194</p>
<p>References 194</p>
<p>6 Monoterpenes and Iridoids 196<br /> Mario Waser and Uwe Rinner</p>
<p>6.1 Introduction 196</p>
<p>6.2 Biosynthesis 196</p>
<p>6.2.1 A cyclic Monoterpenes 197</p>
<p>6.2.2 Cyclic Monoterpenes 197</p>
<p>6.2.3 Iridoids 200</p>
<p>6.2.4 Irregular Monoterpenes 202</p>
<p>6.3 A symmetric Organocatalysis 203</p>
<p>6.3.1 Introduction and Historical Background 204</p>
<p>6.3.2 Enamine, Iminium, and Singly Occupied Molecular Orbital Activation 207</p>
<p>6.3.3 Chiral (Bronsted) Acids and H Bonding Donors 213</p>
<p>6.3.4 Chiral Bronsted/Lewis Bases and Nucleophilic Catalysis 218</p>
<p>6.3.5 A symmetric Phase Transfer Catalysis 220</p>
<p>6.4 O rganocatalysis in the Total Synthesis of Iridoids and Monoterpenoid Indole Alkaloids 225</p>
<p>6.4.1 (+) Geniposide and 7 Deoxyloganin 226</p>
<p>6.4.2 ( ) Brasoside and ( ) Littoralisone 227</p>
<p>6.4.3 (+) Mitsugashiwalactone 229</p>
<p>6.4.4 A lstoscholarine 229</p>
<p>6.4.5 (+) Aspidospermidine and (+) Vincadifformine 230</p>
<p>6.4.6 (+) Yohimbine 230</p>
<p>6.5 Conclusion 231</p>
<p>References 231</p>
<p>7 Sesquiterpenes 236<br /> Alexandros L. Zografos and Elissavet E. Anagnostaki</p>
<p>7.1 Biosynthesis 236</p>
<p>7.2 Cycloisomerization Reactions in Organic Synthesis 244</p>
<p>7.2.1 Enyne Cycloisomerization 245</p>
<p>7.2.2 Diene Cycloisomerization 257</p>
<p>7.3 Application of Cycloisomerizations in the Total Synthesis of Sesquiterpenoids 266</p>
<p>7.3.1 Picrotoxane Sesquiterpenes 266</p>
<p>7.3.2 A romadendrane Sesquiterpenes: Epiglobulol 267</p>
<p>7.3.3 Cubebol Cubebenes Sesquiterpenes 267</p>
<p>7.3.4 Ventricos 7(13) ene 270</p>
<p>7.3.5 Englerins 271</p>
<p>7.3.6 Echinopines 271</p>
<p>7.3.7 Cyperolone 273</p>
<p>7.3.8 Diverse Sesquiterpenoids 276</p>
<p>7.4 Conclusion 276</p>
<p>References 276</p>
<p>8 Diterpenes 279<br /> Louis Barriault</p>
<p>8.1 Introduction 279</p>
<p>8.2 Biosynthesis of Diterpenes Based on Cationic Cyclizations 1,2 Shifts, and Transannular Processes 279</p>
<p>8.3 Pericyclic Reactions and their Application in the Synthesis of Selected Diterpenoids 284</p>
<p>8.3.1 Diels Alder Reaction and Its Application in the Total Synthesis of Diterpenes 284</p>
<p>8.3.2 Cascade Pericyclic Reactions and their Application in the Total Synthesis of Diterpenes 291</p>
<p>8.4 Conclusion 293</p>
<p>References 294</p>
<p>9 Higher Terpenes and Steroids 296<br /> Kazuaki Ishihara</p>
<p>9.1 Introduction 296</p>
<p>9.2 Biosynthesis 296</p>
<p>9.3 Cascade Polyene Cyclizations 303</p>
<p>9.3.1 Diastereoselective Polyene Cyclizations 303</p>
<p>9.3.2 Chiral proton (H+) Induced Polyene Cyclizations 304</p>
<p>9.3.3 Chiral Metal Ion Induced Polyene Cyclizations 308</p>
<p>9.3.4 Chiral Halonium Ion (X+) Induced Polyene Cyclizations 313</p>
<p>9.3.5 Chiral Carbocation Induced Polyene Cyclizations 319</p>
<p>9.3.6 Stereoselective Cyclizations of Homo(polyprenyl)arene Analogs 319</p>
<p>9.4 Biomimetic Total Synthesis of Terpenes and Steroids through Polyene Cyclization 319</p>
<p>9.5 Conclusion 328</p>
<p>References 328</p>
<p>SECTION III SHIKIMIC ACID BIOSYNTHETIC PATHWAY 331</p>
<p>10 Lignans, Lignins, and Resveratrols 333<br /> Yu Peng</p>
<p>10.1 Biosynthesis 333</p>
<p>10.1.1 Primary Metabolism of Shikimic Acid and Aromatic Amino Acids 333</p>
<p>10.1.2 Lignans and Lignin 335</p>
<p>10.2 Auxiliary Assisted C(sp3) H Arylation Reactions in Organic Synthesis 336</p>
<p>10.3 Friedel Crafts Reactions in Organic Synthesis 344</p>
<p>10.4 Total Synthesis of Lignans by C(sp3) H Arylation Reactions 353</p>
<p>10.5 Total Synthesis of Lignans and Polymeric Resveratrol by Friedel Crafts Reactions 357</p>
<p>10.6 Conclusion 375</p>
<p>References 376</p>
<p>SECTION IV MIXED BIOSYNTHETIC PATHWAYS THE STORY OF ALKALOIDS 381</p>
<p>11 Ornithine and Lysine Alkaloids 383<br /> Sebastian Brauch, Wouter S. Veldmate, and Floris P. J. T. Rutjes</p>
<p>11.1 Biosynthesis of l Ornithine and l Lysine Alkaloids 383</p>
<p>11.1.1 Biosynthetic Formation of Alkaloids Derived from l Ornithine 383</p>
<p>11.1.2 Biosynthetic Formation of Alkaloids Derived from l Lysine 388</p>
<p>11.2 The Asymmetric Mannich Reaction in Organic Synthesis 392</p>
<p>11.2.1 Chiral Amines as Catalysts in Asymmetric Mannich Reactions 394</p>
<p>11.2.2 Chiral Bronsted Bases as Catalysts in Asymmetric Mannich Reactions 398</p>
<p>11.2.3 Chiral Bronsted Acids as Catalysts in Asymmetric Mannich Reactions 404</p>
<p>11.2.4 Organometallic Catalysts in Asymmetric Mannich Reactions 408</p>
<p>11.2.5 Biocatalytic Asymmetric Mannich Reactions 413</p>
<p>11.3 Mannich and Related Reactions in the Total Synthesis of l Lysine and l Ornithine Derived Alkaloids 414</p>
<p>11.4 Conclusion 426</p>
<p>References 427</p>
<p>12 Tyrosine Alkaloids 431<br /> Uwe Rinner and Mario Waser</p>
<p>12.1 Introduction 431</p>
<p>12.2 Biosynthesis of Tyrosine Derived Alkaloids 431</p>
<p>12.2.1 Phenylethylamines 431</p>
<p>12.2.2 Simple Tetrahydroisoquinoline Alkaloids 433</p>
<p>12.2.3 Modified Benzyltetrahydroisoquinoline Alkaloids 433</p>
<p>12.2.4 Phenethylisoquinoline Alkaloids 436</p>
<p>12.2.5 Amaryllidaceae Alkaloids 438</p>
<p>12.2.6 Biosynthetic Overview of Tyrosine Derived Alkaloids 442</p>
<p>12.3 Aryl Aryl Coupling Reactions 442</p>
<p>12.3.1 Copper Mediated Aryl Aryl Bond Forming Reactions 443</p>
<p>12.3.2 Nickel Mediated Aryl Aryl Bond Forming Reactions 446</p>
<p>12.3.3 Palladium Mediated Aryl Aryl Bond Forming Reactions 447</p>
<p>12.3.4 Transition Metal Catalyzed Couplings of Nonactivated Aryl Compounds 450</p>
<p>12.4 Synthesis of Tyrosine Derived Alkaloids 456</p>
<p>12.4.1 Synthesis of Modified Benzyltetrahydroisoquinoline Alkaloids 456</p>
<p>12.4.2 Synthesis of Phenethylisoquinoline Alkaloids 460</p>
<p>12.4.3 Synthesis of Amaryllidaceae Alkaloids 462</p>
<p>12.5 Conclusion 468</p>
<p>References 469</p>
<p>13 Histidine and Histidine Like Alkaloids 473<br /> Ian S. Young</p>
<p>13.1 Introduction 473</p>
<p>13.2 Biosynthesis 473</p>
<p>13.3 Atom Economy and Protecting Group Free Chemistry 480</p>
<p>13.4 Challenging the Boundaries of Synthesis: Pias 488</p>
<p>13.5 Conclusion 497</p>
<p>References 499</p>
<p>14 Anthranilic Acid Tryptophan Alkaloids 502<br /> Zhen Yu Tang</p>
<p>14.1 Biosynthesis 502</p>
<p>14.2 Divergent Synthesis Collective Total Synthesis 508</p>
<p>14.3 Collective Total Synthesis of Tryptophan Derived Alkaloids 510</p>
<p>14.3.1 Monoterpene Indole Alkaloids 510</p>
<p>14.3.2 Bisindole Alkaloids 512</p>
<p>References 517</p>
<p>15 Future Directions of Modern Organic Synthesis 519<br /> Jakob Pletz and Rolf Breinbauer</p>
<p>15.1 Introduction 519</p>
<p>15.2 Enzymes in Organic Synthesis: Merging Total Synthesis with Biosynthesis 520</p>
<p>15.3 Engineered Biosynthesis 526</p>
<p>15.4 Diversity Oriented Synthesis, Biology Oriented Synthesis, and Diverted Total Synthesis 533</p>
<p>15.4.1 Diversity oriented Synthesis 535</p>
<p>15.4.2 Biology oriented Synthesis 536</p>
<p>15.4.3 Diverted Total Synthesis 539</p>
<p>15.5 Conclusion 541</p>
<p>References 545</p>
<p>INDEX 548</p>
<p>PREFACE xv</p>
<p>1 From Biosyntheses to Total Syntheses: An Introduction 1<br /> Bastien Nay and Xu Wen Li</p>
<p>1.1 From Primary to Secondary Metabolism: the Key Building Blocks 1</p>
<p>1.1.1 Definitions 1</p>
<p>1.1.2 Energy Supply and Carbon Storing at the Early Stage of Metabolisms 1</p>
<p>1.1.3 Glucose as a Starting Material Toward Key Building Blocks of the Secondary Metabolism 1</p>
<p>1.1.4 Reactions Involved in the Construction of Secondary Metabolites 3</p>
<p>1.1.5 Secondary Metabolisms 4</p>
<p>1.2 From Biosynthesis to Total Synthesis: Strategies Toward the Natural Product Chemical Space 10</p>
<p>1.2.1 The Chemical Space of Natural Products 10</p>
<p>1.2.2 The Biosynthetic Pathways as an Inspiration for Synthetic Challenges 11</p>
<p>1.2.3 The Science of Total Synthesis 14</p>
<p>1.2.4 Conclusion: a Journey in the Future of Total Synthesis 16</p>
<p>References 16</p>
<p>SECTION I ACETATE BIOSYNTHETIC PATHWAY 19</p>
<p>2 Polyketides 21<br /> Françoise Schaefers, Tobias A. M. Gulder, Cyril Bressy, Michael Smietana, Erica Benedetti, Stellios Arseniyadis, Markus Kalesse, and Martin Cordes</p>
<p>2.1 Polyketide Biosynthesis 21</p>
<p>2.1.1 Introduction 21</p>
<p>2.1.2 Assembly of Acetate/Malonate Derived Metabolites 23</p>
<p>2.1.3 Classification of Polyketide Biosynthetic Machineries 23</p>
<p>2.1.4 Conclusion 39</p>
<p>References 40</p>
<p>2.2 Synthesis of Polyketides 44</p>
<p>2.2.1 Asymmetric Alkylation Reactions 44</p>
<p>2.2.2 Applications of Asymmetric Alkylation Reactions in Total Synthesis of Polyketides and Macrolides 60</p>
<p>References 83</p>
<p>2.3 Synthesis of Polyketides Focus on Macrolides 87</p>
<p>2.3.1 Introduction 87</p>
<p>2.3.2 Stereoselective Synthesis of 1,3 Diols: Asymmetric Aldol Reactions 88</p>
<p>2.3.3 Stereoselective Synthesis of 1,3 Diols: Asymmetric Reductions 106</p>
<p>2.3.4 Application of Stereoselective Synthesis of 1,3 Diols in the Total Synthesis of Macrolides 117</p>
<p>2.3.5 Conclusion 126</p>
<p>References 126</p>
<p>3 Fatty Acids and their Derivatives 130<br /> Anders Vik and Trond Vidar Hansen</p>
<p>3.1 Introduction 130</p>
<p>3.2 Biosynthesis 130</p>
<p>3.2.1 Fatty Acids and Lipids 130</p>
<p>3.2.2 Polyunsaturated Fatty Acids 134</p>
<p>3.2.3 Mediated Oxidations of 3 and 6 Polyunsaturated Fatty Acids 135</p>
<p>3.3 Synthesis of 3 and 6 All Z Polyunsaturated Fatty Acids 140</p>
<p>3.3.1 Synthesis of Polyunsaturated Fatty Acids by the Wittig Reaction or by the Polyyne Semihydrogenation 140</p>
<p>3.3.2 Synthesis of Polyunsaturated Fatty Acids via Cross Coupling Reactions 143</p>
<p>3.4 A pplications in Total Synthesis of Polyunsaturated Fatty Acids 145</p>
<p>3.4.1 Palladium Catalyzed Cross Coupling Reactions 145</p>
<p>3.4.2 Biomimetic Transformations of Polyunsaturated Fatty Acids 149</p>
<p>3.4.3 Landmark Total Syntheses 153</p>
<p>3.4.4 Synthesis of Leukotriene B5 158</p>
<p>3.5 Conclusion 160</p>
<p>Acknowledgments 160</p>
<p>References 160</p>
<p>4 Polyethers 162<br /> Youwei Xie and Paul E. Floreancig</p>
<p>4.1 Introduction 162</p>
<p>4.2 Biosynthesis 162</p>
<p>4.2.1 Ionophore Antibiotics 162</p>
<p>4.2.2 Marine Ladder Toxins 165</p>
<p>4.2.3 A nnonaceous Acetogenins and Terpene Polyethers 165</p>
<p>4.3 Epoxide Reactivity and Stereoselective Synthesis 166</p>
<p>4.3.1 Regiocontrol in Epoxide Opening Reactions 166</p>
<p>4.3.2 Stereoselective Epoxide Synthesis 172</p>
<p>4.4 A pplications to Total Synthesis 176</p>
<p>4.4.1 Acid Mediated Transformations 176</p>
<p>4.4.2 Cascades via Epoxonium Ion Formation 179</p>
<p>4.4.3 Cyclizations under Basic Conditions 181</p>
<p>4.4.4 Cyclization in Water 182</p>
<p>4.5 Conclusions 183</p>
<p>References 184</p>
<p>SECTION II MEVALONATE BIOSYNTHETIC PATHWAY 187</p>
<p>5 From Acetate to Mevalonate and Deoxyxylulose Phosphate Biosynthetic Pathways: an Introduction to Terpenoids 189<br /> Alexandros L. Zografos and Elissavet E. Anagnostaki</p>
<p>5.1 Introduction 189</p>
<p>5.2 Mevalonic Acid Pathway 191</p>
<p>5.3 Mevalonate Independent Pathway 192</p>
<p>5.4 Conclusion 194</p>
<p>References 194</p>
<p>6 Monoterpenes and Iridoids 196<br /> Mario Waser and Uwe Rinner</p>
<p>6.1 Introduction 196</p>
<p>6.2 Biosynthesis 196</p>
<p>6.2.1 A cyclic Monoterpenes 197</p>
<p>6.2.2 Cyclic Monoterpenes 197</p>
<p>6.2.3 Iridoids 200</p>
<p>6.2.4 Irregular Monoterpenes 202</p>
<p>6.3 A symmetric Organocatalysis 203</p>
<p>6.3.1 Introduction and Historical Background 204</p>
<p>6.3.2 Enamine, Iminium, and Singly Occupied Molecular Orbital Activation 207</p>
<p>6.3.3 Chiral (Bronsted) Acids and H Bonding Donors 213</p>
<p>6.3.4 Chiral Bronsted/Lewis Bases and Nucleophilic Catalysis 218</p>
<p>6.3.5 A symmetric Phase Transfer Catalysis 220</p>
<p>6.4 O rganocatalysis in the Total Synthesis of Iridoids and Monoterpenoid Indole Alkaloids 225</p>
<p>6.4.1 (+) Geniposide and 7 Deoxyloganin 226</p>
<p>6.4.2 ( ) Brasoside and ( ) Littoralisone 227</p>
<p>6.4.3 (+) Mitsugashiwalactone 229</p>
<p>6.4.4 A lstoscholarine 229</p>
<p>6.4.5 (+) Aspidospermidine and (+) Vincadifformine 230</p>
<p>6.4.6 (+) Yohimbine 230</p>
<p>6.5 Conclusion 231</p>
<p>References 231</p>
<p>7 Sesquiterpenes 236<br /> Alexandros L. Zografos and Elissavet E. Anagnostaki</p>
<p>7.1 Biosynthesis 236</p>
<p>7.2 Cycloisomerization Reactions in Organic Synthesis 244</p>
<p>7.2.1 Enyne Cycloisomerization 245</p>
<p>7.2.2 Diene Cycloisomerization 257</p>
<p>7.3 Application of Cycloisomerizations in the Total Synthesis of Sesquiterpenoids 266</p>
<p>7.3.1 Picrotoxane Sesquiterpenes 266</p>
<p>7.3.2 A romadendrane Sesquiterpenes: Epiglobulol 267</p>
<p>7.3.3 Cubebol Cubebenes Sesquiterpenes 267</p>
<p>7.3.4 Ventricos 7(13) ene 270</p>
<p>7.3.5 Englerins 271</p>
<p>7.3.6 Echinopines 271</p>
<p>7.3.7 Cyperolone 273</p>
<p>7.3.8 Diverse Sesquiterpenoids 276</p>
<p>7.4 Conclusion 276</p>
<p>References 276</p>
<p>8 Diterpenes 279<br /> Louis Barriault</p>
<p>8.1 Introduction 279</p>
<p>8.2 Biosynthesis of Diterpenes Based on Cationic Cyclizations 1,2 Shifts, and Transannular Processes 279</p>
<p>8.3 Pericyclic Reactions and their Application in the Synthesis of Selected Diterpenoids 284</p>
<p>8.3.1 Diels Alder Reaction and Its Application in the Total Synthesis of Diterpenes 284</p>
<p>8.3.2 Cascade Pericyclic Reactions and their Application in the Total Synthesis of Diterpenes 291</p>
<p>8.4 Conclusion 293</p>
<p>References 294</p>
<p>9 Higher Terpenes and Steroids 296<br /> Kazuaki Ishihara</p>
<p>9.1 Introduction 296</p>
<p>9.2 Biosynthesis 296</p>
<p>9.3 Cascade Polyene Cyclizations 303</p>
<p>9.3.1 Diastereoselective Polyene Cyclizations 303</p>
<p>9.3.2 Chiral proton (H+) Induced Polyene Cyclizations 304</p>
<p>9.3.3 Chiral Metal Ion Induced Polyene Cyclizations 308</p>
<p>9.3.4 Chiral Halonium Ion (X+) Induced Polyene Cyclizations 313</p>
<p>9.3.5 Chiral Carbocation Induced Polyene Cyclizations 319</p>
<p>9.3.6 Stereoselective Cyclizations of Homo(polyprenyl)arene Analogs 319</p>
<p>9.4 Biomimetic Total Synthesis of Terpenes and Steroids through Polyene Cyclization 319</p>
<p>9.5 Conclusion 328</p>
<p>References 328</p>
<p>SECTION III SHIKIMIC ACID BIOSYNTHETIC PATHWAY 331</p>
<p>10 Lignans, Lignins, and Resveratrols 333<br /> Yu Peng</p>
<p>10.1 Biosynthesis 333</p>
<p>10.1.1 Primary Metabolism of Shikimic Acid and Aromatic Amino Acids 333</p>
<p>10.1.2 Lignans and Lignin 335</p>
<p>10.2 Auxiliary Assisted C(sp3) H Arylation Reactions in Organic Synthesis 336</p>
<p>10.3 Friedel Crafts Reactions in Organic Synthesis 344</p>
<p>10.4 Total Synthesis of Lignans by C(sp3) H Arylation Reactions 353</p>
<p>10.5 Total Synthesis of Lignans and Polymeric Resveratrol by Friedel Crafts Reactions 357</p>
<p>10.6 Conclusion 375</p>
<p>References 376</p>
<p>SECTION IV MIXED BIOSYNTHETIC PATHWAYS THE STORY OF ALKALOIDS 381</p>
<p>11 Ornithine and Lysine Alkaloids 383<br /> Sebastian Brauch, Wouter S. Veldmate, and Floris P. J. T. Rutjes</p>
<p>11.1 Biosynthesis of l Ornithine and l Lysine Alkaloids 383</p>
<p>11.1.1 Biosynthetic Formation of Alkaloids Derived from l Ornithine 383</p>
<p>11.1.2 Biosynthetic Formation of Alkaloids Derived from l Lysine 388</p>
<p>11.2 The Asymmetric Mannich Reaction in Organic Synthesis 392</p>
<p>11.2.1 Chiral Amines as Catalysts in Asymmetric Mannich Reactions 394</p>
<p>11.2.2 Chiral Bronsted Bases as Catalysts in Asymmetric Mannich Reactions 398</p>
<p>11.2.3 Chiral Bronsted Acids as Catalysts in Asymmetric Mannich Reactions 404</p>
<p>11.2.4 Organometallic Catalysts in Asymmetric Mannich Reactions 408</p>
<p>11.2.5 Biocatalytic Asymmetric Mannich Reactions 413</p>
<p>11.3 Mannich and Related Reactions in the Total Synthesis of l Lysine and l Ornithine Derived Alkaloids 414</p>
<p>11.4 Conclusion 426</p>
<p>References 427</p>
<p>12 Tyrosine Alkaloids 431<br /> Uwe Rinner and Mario Waser</p>
<p>12.1 Introduction 431</p>
<p>12.2 Biosynthesis of Tyrosine Derived Alkaloids 431</p>
<p>12.2.1 Phenylethylamines 431</p>
<p>12.2.2 Simple Tetrahydroisoquinoline Alkaloids 433</p>
<p>12.2.3 Modified Benzyltetrahydroisoquinoline Alkaloids 433</p>
<p>12.2.4 Phenethylisoquinoline Alkaloids 436</p>
<p>12.2.5 Amaryllidaceae Alkaloids 438</p>
<p>12.2.6 Biosynthetic Overview of Tyrosine Derived Alkaloids 442</p>
<p>12.3 Aryl Aryl Coupling Reactions 442</p>
<p>12.3.1 Copper Mediated Aryl Aryl Bond Forming Reactions 443</p>
<p>12.3.2 Nickel Mediated Aryl Aryl Bond Forming Reactions 446</p>
<p>12.3.3 Palladium Mediated Aryl Aryl Bond Forming Reactions 447</p>
<p>12.3.4 Transition Metal Catalyzed Couplings of Nonactivated Aryl Compounds 450</p>
<p>12.4 Synthesis of Tyrosine Derived Alkaloids 456</p>
<p>12.4.1 Synthesis of Modified Benzyltetrahydroisoquinoline Alkaloids 456</p>
<p>12.4.2 Synthesis of Phenethylisoquinoline Alkaloids 460</p>
<p>12.4.3 Synthesis of Amaryllidaceae Alkaloids 462</p>
<p>12.5 Conclusion 468</p>
<p>References 469</p>
<p>13 Histidine and Histidine Like Alkaloids 473<br /> Ian S. Young</p>
<p>13.1 Introduction 473</p>
<p>13.2 Biosynthesis 473</p>
<p>13.3 Atom Economy and Protecting Group Free Chemistry 480</p>
<p>13.4 Challenging the Boundaries of Synthesis: Pias 488</p>
<p>13.5 Conclusion 497</p>
<p>References 499</p>
<p>14 Anthranilic Acid Tryptophan Alkaloids 502<br /> Zhen Yu Tang</p>
<p>14.1 Biosynthesis 502</p>
<p>14.2 Divergent Synthesis Collective Total Synthesis 508</p>
<p>14.3 Collective Total Synthesis of Tryptophan Derived Alkaloids 510</p>
<p>14.3.1 Monoterpene Indole Alkaloids 510</p>
<p>14.3.2 Bisindole Alkaloids 512</p>
<p>References 517</p>
<p>15 Future Directions of Modern Organic Synthesis 519<br /> Jakob Pletz and Rolf Breinbauer</p>
<p>15.1 Introduction 519</p>
<p>15.2 Enzymes in Organic Synthesis: Merging Total Synthesis with Biosynthesis 520</p>
<p>15.3 Engineered Biosynthesis 526</p>
<p>15.4 Diversity Oriented Synthesis, Biology Oriented Synthesis, and Diverted Total Synthesis 533</p>
<p>15.4.1 Diversity oriented Synthesis 535</p>
<p>15.4.2 Biology oriented Synthesis 536</p>
<p>15.4.3 Diverted Total Synthesis 539</p>
<p>15.5 Conclusion 541</p>
<p>References 545</p>
<p>INDEX 548</p>