Elsevier S & T

Strategies and Tactics in Organic Synthesis

Harmata, Michael

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Table of contents
  • Cover
  • Contentsv
  • Contributorsxv
  • Forewordxix
  • Prefacexxi
  • Dedicationxxiii
  • CHAPTER 1. THE TOTAL SYNTHESIS OF LUZOPEPTINS1
  • I. Introduction1
  • II. Background3
  • III. Synthesis of Quinaldic Acid and gly-sar-mhv Tripeptide Fragments7
  • IV. Synthesis and Chemistry of the Piperazic Acid Fragment12
  • V. Initial Cyclization Experiments23
  • VI. The Total Synthesis26
  • VII. Epilogue31
  • VIII. Acknowledgements33
  • References and Footnotes33
  • CHAPTER 2. SYNTHESIS OF GELDANAMYCIN USING GLYCOLATE ALDOL REACTIONS38
  • I. Introduction38
  • II. Retrosynthetic Analysis39
  • III. Ansamycin Antitumor Antibiotics41
  • IV. Synthesis of the C12-C21 Quinone Precursor Portion using Evans Asymmetric Alkylation45
  • V. Development of Anti-Selective Glycolate Aldol Methodology Based on the 2,3-Diaryl l,4-Dioxan-5-on47
  • VI. Installation of the C11-12 Hydroxy Methoxy Functionality49
  • VII. Difficulties Associated with the C10 methyl and the C8-9 Trisubstituted Alkene51
  • VIII. Syn Glycolate Aldol Methodology Based on the Masamune Norephedrine Auxiliary53
  • IX. Construction of the C2-5 Diene and Macrolactamization55
  • X. Unsuccessful RCM-Based Convergent Approach58
  • XI. Unanticipated Problematic Para-Quinone Formation59
  • XII. Successful Strategy for Para-Quinone formation Using a 1,4-Di-Protected Hydroquinone Precursor64
  • XIII. Conclusions66
  • References and Footnotes67
  • CHAPTER 3. FROM METHYLENE BRIDGED GLYCOLURIL DIMERS TO CUCURBIT[N]URIL ANALOGS WITH SOME DETOURS ALO71
  • I. Introduction71
  • II. Retrosynthetic Analysis of the Cucurbit[n]uril Family74
  • III. A Few Lucky Breaks Lead to C- and S-Shaped Methylene Bridged Glycoluril Dimers75
  • IV. The Hard Work77
  • V. Three Related Synthetic Procedures Lead to S- and C-shaped Methylene Bridged Glycoluril Dimers80
  • VI. Interlude. Molecular Clips Capable of Enantiomeric Self-Recognition, Heterochiral Recognition, a83
  • VII. Implications for the Mechanism of CB[n] Formation and the Synthesis of Cucurbit[n]uril Derivati87
  • VIII. Mechanism of the S- to C-Shaped Interconversion and Implications for the Synthesis of Cucurbit90
  • IX. Methylene Bridged Glycoluril Oligomers93
  • X. Phthalhydrazides are Nucleophilic Glycoluril Surrogates93
  • XI. Cucurbit[n]uril Analogs94
  • XII. Conclusions97
  • References and Footnotes98
  • CHAPTER 4. APPLICATION OF SILICON-ASSISTED INTRAMOLECULAR CROSS-COUPLING IN TOTAL SYNTHESIS OF (+)-B100
  • I. Introduction and Background100
  • II. Preliminary Studies103
  • III. Synthetic Strategies106
  • IV. Synthesis of (+)-Brasilenyne107
  • V. Conformational Analysis125
  • VI. Summary131
  • References and Footnotes133
  • CHAPTER 5. SAMARIUM(II) PROMOTED KETYL OLEFIN CYCLIZATIONS APPLIED TO THE TOTAL SYNTHESES OF (-)-STE137
  • I. Introduction137
  • II. Samarium(II) Promoted Ketyl-Olefin Cyclizations139
  • III. Total Synthesis of (-)-Steganone144
  • IV. Total Synthesis of ( + )-Isoschizandrin155
  • V. Conclusion167
  • References and Footnotes168
  • CHAPTER 6. THE SYNTHESIS OF POLYCAVERNOSIDE A. AN EXAMPLE OF CONFORMATIONALLY GUIDED MACROLACTONIZAT173
  • I. Introduction173
  • II. Polycavernoside A: A Lethal Metabolite from Polycavernosa tsudai175
  • III. First Generation Strategy176
  • IV. Synthesis of a C10-C16 Dithiane Fragment180
  • V. Intramolecular Alkoxy Carbonylation of 6-Hydroxy-l-octenes183
  • VI. Synthesis of a C1-C9 Aldehyde Fragment and Failure of Dithiane Coupling187
  • VII. A Revised Plan: Fragment Umpolung and an Antipodean Target190
  • VIII. Fragment Union by a Nozaki-Hiyama-Kishi (NHK) Reaction192
  • IX. The Quest for a Differentially Protected C10-C16 Aldehyde Fragment196
  • X. Regioselective Macrolactonization of a Trihydroxy Carboxylic Acid199
  • XI. Completion of Aglycon Core: A Formal Synthesis of Polycavernoside A204
  • XII. Coup de Grace. The Realization of Polycavernoside A206
  • XIII. Conclusion207
  • References208
  • CHAPTER 7. FIRST TOTAL SYNTHESIS OF SEVERAL NATURAL PRODUCTS BASED ON ALKYNE-CO2(CO)6 COMPLEXES211
  • I. Introduction211
  • II. First Total Synthesis of (+)-Secosyrins 1 and 2212
  • III. First Total Synthesis of (-)-Ichthyothereol223
  • IV. First Total Synthesis229
  • V. Summary242
  • References and Footnotes242
  • CHAPTER 8. TOTAL SYNTHESIS OF MYRIAPORONES 1,3, AND 4246
  • I. The Foundation: Tedanolide and the Myriaporones246
  • II. An Issue of Timing: A Strategy for the Synthesis of the Myriaporones248
  • III. C9-C13: The Most Elegant Reaction is one That Works Well250
  • IV. C8-C9: The Best Model System is the Natural Substrate250
  • V. Deja Vu All Over Again: Evans Aldol Approach253
  • VI. Hindsight is 20:20: Myriaporone 1 or Myriaporones 3 and 4253
  • VII. A Critical Postponement: Late-Stage Epoxidation and the Targeting of Myriaporones 3 and 4256
  • VIII. Unexpected Myriaporone 1 Formation262
  • IX. Stereochemical Assignment of Myriaporones 1,3, and 4265
  • X. Perspective267
  • References and Footnotes267
  • CHAPTER 9. ADVENTURES IN NATURAL PRODUCT SYNTHESIS. FROM DEEP SEA SPONGE TO PILOT PLANT: THE LARGE S269
  • I. Introduction269
  • II. Comments on the Structure271
  • III. Project Background272
  • IV. Literature Evaluation and Route Selection274
  • V. Execution282
  • VI. Synthesis Statistics313
  • VII. Outlook314
  • VIII. Conclusion and Summary314
  • References and Footnotes317
  • CHAPTER 10. SYNTHESIS OF APREPITANT321
  • I. Introduction321
  • II. Original Medicinal Chemistry Route and Process Research Evaluation321
  • III. Oxazinone Synthesis324
  • IV. Diastereoselective Acetal Formation and Olefin Hydrogenation330
  • V. End Game and Triazolinone Synthesis334
  • VI. Synthesis Revision335
  • VII. 2nd Total Synthesis: Hofmann Elimination337
  • VIII. 3rd Total Synthesis: Trans-Acetalization Reaction339
  • IX. Chiral Alcohol Synthesis343
  • X. 4th Total Synthesis: The Manufacturing Process – Discovery344
  • XI. 4th Total Synthesis: The Manufacturing Process - Optimization345
  • XII. Conclusion349
  • References and Footnotes350
  • CHAPTER 11. TOTAL SYNTHESIS AND MECHANISM OF ACTION STUDIES ON THE ANTITUMOR ALKALOID, (-)-AGELASTAT352
  • I. Introduction: The Challenges Faced by Scientists Involved in 21st Century Genomics Research, and353
  • II. The Discovery of Agelastatin A and its Postulated Biogenesis355
  • III. Initial Biological Screening of (-)-Agelastatin A356
  • IV. Past Total Synthesis Studies on Agelastatin A359
  • V. Our Reasons for Developing a New Total Synthesis of (-)-Agelastatin A363
  • VI. Our Initial Retrosynthetic Plan363
  • VII. Attempted Implementation of Our Initial Strategic Planning for (-)-Agelastatin A365
  • VIII. A Second-Strike Strategy for (-)-Agelastatin A373
  • IX. A Third-Strike Strategy for (-)-Agelastatin A: A Formal Total Synthesis377
  • X. A New Endgame and Total Synthesis of (-)-Agelastatin A381
  • XI. A Preliminary Comparison of the Antitumor Properties of (-)-Agelastatin A and Cisplatin Against388
  • XII. Toxicological Studies on (-)-Agelastatin A388
  • XIII. Preliminary Mechanism of Action Studies on (-)-Agelastatin A389
  • XIV. Conclusions390
  • References and Footnotes391
  • CHAPTER 12. DESIGN AND SYNTHESIS OF COOPERATIVE "PINWHEEL" FLUORESCENT SENSORS395
  • I. Introduction to Cooperative Recognition and Chemical Sensing395
  • II. Synthesis of a Symmetrical Bis-trityl Mono-acetylene Sensor397
  • III. Design of a Second Generation Fluorescent Pinwheel Sensor402
  • IV. General Synthetic Strategy for Fluorescent Bis-trityl Sensors404
  • V. Applications to a Dicarboxylate Sensor408
  • VI. Applications to a Carbohydrate Sensor410
  • VII. Conclusions413
  • References and Footnotes413
  • CHAPTER 13. FUNCTIONALIZATION OF PYRIDINES AND THIAZOLES VIA THE HALOGEN-DANCE REACTION, APPLICATION415
  • I. Introduction415
  • II. The Functionalization of Pyridines - The Halogen-Dance Reaction417
  • III. Retrosynthetic analysis421
  • IV. Early Efforts, Limitations to the 1,3-Halogen-Dance Reaction422
  • V. Successful 1,3-and 1,4-Halogen-Dance Reactions, Synthesis of the Core Pyridine Structure424
  • VI. Completion of the Synthesis of Caerulomycin C425
  • VII. Completion of the Synthesis of WS75624 B, Application of the Halogen-Dance reaction to Thiazole426
  • VIII. Conclusion433
  • References and Footnotes433
  • CHAPTER 14. DIASTEREOSELECTIVE INTRAMOLECULAR 4+3 CYCLOADDITION AND AN ENANTIOSELECTIVE TOTAL SYNTHE437
  • I. Introduction437
  • II. Dactylol438
  • III. 4+3 Cycloaddition Reactions of Cyclic Oxyallyl Zwitterions441
  • IV. Synthesis of Cyclooctanoids via Intramolecular 4+3 Cycloaddition Reactions444
  • V. Diastereocontrol in 4+3 Cycloaddition Reactions448
  • VI. Retrosynthetic Analysis of ( + )-Dactylol449
  • VII. Preparation of the Diene Side Chain450
  • VIII. Preparation of the Cycloaddition Substrate453
  • IX. The Key 4+3 Cycloaddition Reaction454
  • X. From the Cycloadduct to ( + )-Dactylol455
  • XI. Conclusion462
  • References462
  • INDEX465
Book details
  • Vendor Elsevier S & T
  • SKU 9780124502888
  • ISBN-13 9780080541822
  • Author Harmata, Michael
  • Category Science
  • Subject Organic

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A classic in the area of organic synthesis, Strategies and Tactics in Organic Synthesis provides a forum for investigators to discuss their approach to the science and art of organic synthesis. Rather than a simple presentation of data or a second-hand analysis, we are given stories that vividly demonstrate the power of the human endeavour known as organic synthesis and the creativity and tenacity of its practitioners. First hand accounts of each project tell of the excitement of conception, the frustration of failure and the joy experienced when either rational thought and/or good fortune give rise to successful completion of a project. In this book we learn how synthesis is really done and are educated, challenged and inspired by these stories, which portray the idea that triumphs do not come without challenges. We also learn that we can meet challenges to further advance the science and art of organic synthesis, driving it forward to meet the demands of society, in discovering new reactions, creating new designs and building molecules with atom and step economies that provide solutions through function to create a better world.

* Presents state-of-the-art developments in organic synthesis
* Provides insight and offers new perspective to problem-solving
* Written by leading experts in the field