From Biosynthesis to Total Synthesis
John Wiley & Sons Inc (Verlag)
978-1-118-75173-2 (ISBN)
• 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
Alexandros L. Zografos graduated as a chemist from the National and Kapodistrian University of Athens, Greece. After earning his PhD in 2001 at the National Technical University of Athens, he pursued his postdoctoral studies with Prof. Phil Baran at the Scripps Research Institute and Prof. Scott Snyder at Columbia University before he moved back to Greece to work as a senior researcher at the National and Kapodistrian University of Athens and NCRS Demokritos Institute. In 2009, he began his independent career at the Aristotle University of Thessaloniki, Greece, where he is currently an assistant professor of organic chemistry. His group is working on divergent total synthesis of complex natural products and on the development of novel CH activation reactions.
LIST OF CONTRIBUTORS xiii
PREFACE xv
1 From Biosyntheses to Total Syntheses: An Introduction 1
Bastien Nay and Xu‐Wen Li
1.1 From Primary to Secondary Metabolism: the Key Building Blocks 1
1.1.1 Definitions 1
1.1.2 Energy Supply and Carbon Storing at the Early Stage of Metabolisms 1
1.1.3 Glucose as a Starting Material Toward Key Building Blocks of the Secondary Metabolism 1
1.1.4 Reactions Involved in the Construction of Secondary Metabolites 3
1.1.5 Secondary Metabolisms 4
1.2 From Biosynthesis to Total Synthesis: Strategies Toward the Natural Product Chemical Space 10
1.2.1 The Chemical Space of Natural Products 10
1.2.2 The Biosynthetic Pathways as an Inspiration for Synthetic Challenges 11
1.2.3 The Science of Total Synthesis 14
1.2.4 Conclusion: a Journey in the Future of Total Synthesis 16
References 16
SECTION I ACETATE BIOSYNTHETIC PATHWAY 19
2 Polyketides 21
Françoise Schaefers, Tobias A. M. Gulder, Cyril Bressy, Michael Smietana, Erica Benedetti, Stellios Arseniyadis, Markus Kalesse, and Martin Cordes
2.1 Polyketide Biosynthesis 21
2.1.1 Introduction 21
2.1.2 Assembly of Acetate/Malonate‐Derived Metabolites 23
2.1.3 Classification of Polyketide Biosynthetic Machineries 23
2.1.4 Conclusion 39
References 40
2.2 Synthesis of Polyketides 44
2.2.1 Asymmetric Alkylation Reactions 44
2.2.2 Applications of Asymmetric Alkylation Reactions in Total Synthesis of Polyketides and Macrolides 60
References 83
2.3 Synthesis of Polyketides‐Focus on Macrolides 87
2.3.1 Introduction 87
2.3.2 Stereoselective Synthesis of 1,3‐Diols: Asymmetric Aldol Reactions 88
2.3.3 Stereoselective Synthesis of 1,3‐Diols: Asymmetric Reductions 106
2.3.4 Application of Stereoselective Synthesis of 1,3‐Diols in the Total Synthesis of Macrolides 117
2.3.5 Conclusion 126
References 126
3 Fatty Acids and their Derivatives 130
Anders Vik and Trond Vidar Hansen
3.1 Introduction 130
3.2 Biosynthesis 130
3.2.1 Fatty Acids and Lipids 130
3.2.2 Polyunsaturated Fatty Acids 134
3.2.3 Mediated Oxidations of ω‐3 and ω‐6 Polyunsaturated Fatty Acids 135
3.3 Synthesis of ω‐3 and ω‐6 All‐Z Polyunsaturated Fatty Acids 140
3.3.1 Synthesis of Polyunsaturated Fatty Acids by the Wittig Reaction or by the Polyyne Semihydrogenation 140
3.3.2 Synthesis of Polyunsaturated Fatty Acids via Cross Coupling Reactions 143
3.4 A pplications in Total Synthesis of Polyunsaturated Fatty Acids 145
3.4.1 Palladium‐Catalyzed Cross Coupling Reactions 145
3.4.2 Biomimetic Transformations of Polyunsaturated Fatty Acids 149
3.4.3 Landmark Total Syntheses 153
3.4.4 Synthesis of Leukotriene B5 158
3.5 Conclusion 160
Acknowledgments 160
References 160
4 Polyethers 162
Youwei Xie and Paul E. Floreancig
4.1 Introduction 162
4.2 Biosynthesis 162
4.2.1 Ionophore Antibiotics 162
4.2.2 Marine Ladder Toxins 165
4.2.3 A nnonaceous Acetogenins and Terpene Polyethers 165
4.3 Epoxide Reactivity and Stereoselective Synthesis 166
4.3.1 Regiocontrol in Epoxide‐Opening Reactions 166
4.3.2 Stereoselective Epoxide Synthesis 172
4.4 A pplications to Total Synthesis 176
4.4.1 Acid‐Mediated Transformations 176
4.4.2 Cascades via Epoxonium Ion Formation 179
4.4.3 Cyclizations under Basic Conditions 181
4.4.4 Cyclization in Water 182
4.5 Conclusions 183
References 184
SECTION II MEVALONATE BIOSYNTHETIC PATHWAY 187
5 From Acetate to Mevalonate and Deoxyxylulose Phosphate Biosynthetic Pathways: an Introduction to Terpenoids 189
Alexandros L. Zografos and Elissavet E. Anagnostaki
5.1 Introduction 189
5.2 Mevalonic Acid Pathway 191
5.3 Mevalonate‐Independent Pathway 192
5.4 Conclusion 194
References 194
6 Monoterpenes and Iridoids 196
Mario Waser and Uwe Rinner
6.1 Introduction 196
6.2 Biosynthesis 196
6.2.1 A cyclic Monoterpenes 197
6.2.2 Cyclic Monoterpenes 197
6.2.3 Iridoids 200
6.2.4 Irregular Monoterpenes 202
6.3 A symmetric Organocatalysis 203
6.3.1 Introduction and Historical Background 204
6.3.2 Enamine, Iminium, and Singly Occupied Molecular Orbital Activation 207
6.3.3 Chiral (Bronsted) Acids and H‐Bonding Donors 213
6.3.4 Chiral Bronsted/Lewis Bases and Nucleophilic Catalysis 218
6.3.5 A symmetric Phase‐Transfer Catalysis 220
6.4 O rganocatalysis in the Total Synthesis of Iridoids and Monoterpenoid Indole Alkaloids 225
6.4.1 (+)‐Geniposide and 7‐Deoxyloganin 226
6.4.2 (–)‐Brasoside and (–)‐Littoralisone 227
6.4.3 (+)‐Mitsugashiwalactone 229
6.4.4 A lstoscholarine 229
6.4.5 (+)‐Aspidospermidine and (+)‐Vincadifformine 230
6.4.6 (+)‐Yohimbine 230
6.5 Conclusion 231
References 231
7 Sesquiterpenes 236
Alexandros L. Zografos and Elissavet E. Anagnostaki
7.1 Biosynthesis 236
7.2 Cycloisomerization Reactions in Organic Synthesis 244
7.2.1 Enyne Cycloisomerization 245
7.2.2 Diene Cycloisomerization 257
7.3 Application of Cycloisomerizations in the Total Synthesis of Sesquiterpenoids 266
7.3.1 Picrotoxane Sesquiterpenes 266
7.3.2 A romadendrane Sesquiterpenes: Epiglobulol 267
7.3.3 Cubebol–Cubebenes Sesquiterpenes 267
7.3.4 Ventricos‐7(13)‐ene 270
7.3.5 Englerins 271
7.3.6 Echinopines 271
7.3.7 Cyperolone 273
7.3.8 Diverse Sesquiterpenoids 276
7.4 Conclusion 276
References 276
8 Diterpenes 279
Louis Barriault
8.1 Introduction 279
8.2 Biosynthesis of Diterpenes Based on Cationic Cyclizations 1,2‐Shifts, and Transannular Processes 279
8.3 Pericyclic Reactions and their Application in the Synthesis of Selected Diterpenoids 284
8.3.1 Diels–Alder Reaction and Its Application in the Total Synthesis of Diterpenes 284
8.3.2 Cascade Pericyclic Reactions and their Application in the Total Synthesis of Diterpenes 291
8.4 Conclusion 293
References 294
9 Higher Terpenes and Steroids 296
Kazuaki Ishihara
9.1 Introduction 296
9.2 Biosynthesis 296
9.3 Cascade Polyene Cyclizations 303
9.3.1 Diastereoselective Polyene Cyclizations 303
9.3.2 “Chiral proton (H+)”‐Induced Polyene Cyclizations 304
9.3.3 “Chiral Metal Ion”‐Induced Polyene Cyclizations 308
9.3.4 “Chiral Halonium Ion (X+)”‐Induced Polyene Cyclizations 313
9.3.5 “Chiral Carbocation”‐Induced Polyene Cyclizations 319
9.3.6 Stereoselective Cyclizations of Homo(polyprenyl)arene Analogs 319
9.4 Biomimetic Total Synthesis of Terpenes and Steroids through Polyene Cyclization 319
9.5 Conclusion 328
References 328
SECTION III SHIKIMIC ACID BIOSYNTHETIC PATHWAY 331
10 Lignans, Lignins, and Resveratrols 333
Yu Peng
10.1 Biosynthesis 333
10.1.1 Primary Metabolism of Shikimic Acid and Aromatic Amino Acids 333
10.1.2 Lignans and Lignin 335
10.2 Auxiliary‐Assisted C(sp3)–H Arylation Reactions in Organic Synthesis 336
10.3 Friedel–Crafts Reactions in Organic Synthesis 344
10.4 Total Synthesis of Lignans by C(sp3)─H Arylation Reactions 353
10.5 Total Synthesis of Lignans and Polymeric Resveratrol by Friedel–Crafts Reactions 357
10.6 Conclusion 375
References 376
SECTION IV MIXED BIOSYNTHETIC PATHWAYS–THE STORY OF ALKALOIDS 381
11 Ornithine and Lysine Alkaloids 383
Sebastian Brauch, Wouter S. Veldmate, and Floris P. J. T. Rutjes
11.1 Biosynthesis of l‐Ornithine and l‐Lysine Alkaloids 383
11.1.1 Biosynthetic Formation of Alkaloids Derived from l‐Ornithine 383
11.1.2 Biosynthetic Formation of Alkaloids Derived from l‐Lysine 388
11.2 The Asymmetric Mannich Reaction in Organic Synthesis 392
11.2.1 Chiral Amines as Catalysts in Asymmetric Mannich Reactions 394
11.2.2 Chiral Bronsted Bases as Catalysts in Asymmetric Mannich Reactions 398
11.2.3 Chiral Bronsted Acids as Catalysts in Asymmetric Mannich Reactions 404
11.2.4 Organometallic Catalysts in Asymmetric Mannich Reactions 408
11.2.5 Biocatalytic Asymmetric Mannich Reactions 413
11.3 Mannich and Related Reactions in the Total Synthesis of l‐Lysine‐ and l‐Ornithine‐Derived Alkaloids 414
11.4 Conclusion 426
References 427
12 Tyrosine Alkaloids 431
Uwe Rinner and Mario Waser
12.1 Introduction 431
12.2 Biosynthesis of Tyrosine‐Derived Alkaloids 431
12.2.1 Phenylethylamines 431
12.2.2 Simple Tetrahydroisoquinoline Alkaloids 433
12.2.3 Modified Benzyltetrahydroisoquinoline Alkaloids 433
12.2.4 Phenethylisoquinoline Alkaloids 436
12.2.5 Amaryllidaceae Alkaloids 438
12.2.6 Biosynthetic Overview of Tyrosine‐Derived Alkaloids 442
12.3 Aryl–Aryl Coupling Reactions 442
12.3.1 Copper‐Mediated Aryl–Aryl Bond Forming Reactions 443
12.3.2 Nickel‐Mediated Aryl–Aryl Bond Forming Reactions 446
12.3.3 Palladium‐Mediated Aryl–Aryl Bond Forming Reactions 447
12.3.4 Transition Metal‐Catalyzed Couplings of Nonactivated Aryl Compounds 450
12.4 Synthesis of Tyrosine‐Derived Alkaloids 456
12.4.1 Synthesis of Modified Benzyltetrahydroisoquinoline Alkaloids 456
12.4.2 Synthesis of Phenethylisoquinoline Alkaloids 460
12.4.3 Synthesis of Amaryllidaceae Alkaloids 462
12.5 Conclusion 468
References 469
13 Histidine and Histidine‐Like Alkaloids 473
Ian S. Young
13.1 Introduction 473
13.2 Biosynthesis 473
13.3 Atom Economy and Protecting‐Group‐Free Chemistry 480
13.4 Challenging the Boundaries of Synthesis: Pias 488
13.5 Conclusion 497
References 499
14 Anthranilic Acid–Tryptophan Alkaloids 502
Zhen‐Yu Tang
14.1 Biosynthesis 502
14.2 Divergent Synthesis–Collective Total Synthesis 508
14.3 Collective Total Synthesis of Tryptophan‐Derived Alkaloids 510
14.3.1 Monoterpene Indole Alkaloids 510
14.3.2 Bisindole Alkaloids 512
References 517
15 Future Directions of Modern Organic Synthesis 519
Jakob Pletz and Rolf Breinbauer
15.1 Introduction 519
15.2 Enzymes in Organic Synthesis: Merging Total Synthesis with Biosynthesis 520
15.3 Engineered Biosynthesis 526
15.4 Diversity‐Oriented Synthesis, Biology‐Oriented Synthesis, and Diverted Total Synthesis 533
15.4.1 Diversity‐oriented Synthesis 535
15.4.2 Biology‐oriented Synthesis 536
15.4.3 Diverted Total Synthesis 539
15.5 Conclusion 541
References 545
INDEX 548
| Erscheinungsdatum | 14.05.2016 |
|---|---|
| Verlagsort | New York |
| Sprache | englisch |
| Maße | 206 x 279 mm |
| Gewicht | 1588 g |
| Themenwelt | Naturwissenschaften ► Biologie ► Biochemie |
| Naturwissenschaften ► Chemie ► Organische Chemie | |
| ISBN-10 | 1-118-75173-6 / 1118751736 |
| ISBN-13 | 978-1-118-75173-2 / 9781118751732 |
| Zustand | Neuware |
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