Harmata Strategies and Tactics in Organic Synthesis

1. Auflage 2005
ISBN: 978-0-08-045884-7
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 500 Seiten, Web PDF

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

Autoren/Hrsg.

Harmata, Michael

Inhaltsverzeichnis

1;COVER;1
2;STRATEGIES AND TACTICS IN ORGANIC SYNTHESIS;4
3;Copyright Page;5
4;CONTENTS;6
5;CONTRIBUTORS;16
6;Foreword;20
7;Preface;22
8;Dedication;24
9;CHAPTER 1. THE TOTAL SYNTHESIS OF LUZOPEPTINS;26
9.1;I. Introduction;26
9.2;II. Background;28
9.3;III. Synthesis of Quinaldic Acid and gly-sar-mhv Tripeptide Fragments;32
9.4;IV. Synthesis and Chemistry of the Piperazic Acid Fragment;37
9.5;V. Initial Cyclization Experiments;48
9.6;VI. The Total Synthesis;51
9.7;VII. Epilogue;56
9.8;VIII. Acknowledgements;58
9.9;References and Footnotes;58
10;CHAPTER 2. SYNTHESIS OF GELDANAMYCIN USING GLYCOLATE ALDOL REACTIONS;63
10.1;I. Introduction;63
10.2;II. Retrosynthetic Analysis;64
10.3;III. Ansamycin Antitumor Antibiotics;66
10.4;IV. Synthesis of the C12-C21 Quinone Precursor Portion using Evans Asymmetric Alkylation;70
10.5;V. Development of Anti-Selective Glycolate Aldol Methodology Based on the 2,3-Diary1 1,4-Dioxan-5-one Template;72
10.6;VI. Installation of the C11-12 Hydroxy Methoxy Functionality;74
10.7;VII. Difficulties Associated with the C10 methyl and the C8-9 Trisubstituted Alkene;76
10.8;VIII. Syn Glycolate Aldol Methodology Based on the Masamune Norephedrine Auxiliary;78
10.9;IX. Construction of the C2-5 Diene and Macrolactamization;80
10.10;X. Unsuccessful RCM-Based Convergent Approach;83
10.11;XI. Unanticipated Problematic Para-Quinone Formation;84
10.12;XII. Successful Strategy for Para-Quinone formation Using a 1,4-Di-Protected Hydroquinone Precursor;89
10.13;XIII. Conclusions;91
10.14;References and Footnotes;92
11;CHAPTER 3. FROM METHYLENE BRIDGED GLYCOLURIL DIMERS TO CUCURBIT[N]URIL ANALOGS WITH SOME DETOURS ALONG THE WAY;96
11.1;I. Introduction;96
11.2;II. Retrosynthetic Analysis of the Cucurbit[n]uril Family;99
11.3;III. A Few Lucky Breaks Lead to C- and S-Shaped Methylene Bridged Glycoluril Dimers;100
11.4;IV. The Hard Work;102
11.5;V. Three Related Synthetic Procedures Lead to S- and C-shaped Methylene Bridged Glycoluril Dimers;105
11.6;VI. Interlude. Molecular Clips Capable of Enantiomeric Self-Recognition, Heterochiral Recognition, and Self-Sorting;108
11.7;VII. Implications for the Mechanism of CB[n] Formation and the Synthesis of Cucurbit[n]uril Derivatives;112
11.8;VIII. Mechanism of the S- to C-Shaped Interconversion and Implications for the Synthesis of Cucurbit[n]uril Derivatives;115
11.9;IX. Methylene Bridged Glycoluril Oligomers;118
11.10;X. Phthalhydrazides are Nucleophilic Glycoluril Surrogates;118
11.11;XI. Cucurbit[n]uril Analogs;119
11.12;XII. Conclusions;122
11.13;References and Footnotes;123
12;CHAPTER 4. APPLICATION OF SILICON-ASSISTED INTRAMOLECULAR CROSS-COUPLING IN TOTAL SYNTHESIS OF (+)-BRASILENYNE;125
12.1;I. Introduction and Background;125
12.2;II. Preliminary Studies;128
12.3;III. Synthetic Strategies;131
12.4;IV. Synthesis of (+)-Brasilenyne;132
12.5;V. Conformational Analysis;150
12.6;VI. Summary;156
12.7;References and Footnotes;158
13;CHAPTER 5. SAMARIUM(II) PROMOTED KETYL OLEFIN CYCLIZATIONS APPLIED TO THE TOTAL SYNTHESES OF (-)-STEGANONE AND (+)-ISOSCHIZANDRIN;162
13.1;I. Introduction;162
13.2;II. Samarium(II) Promoted Ketyl-Olefin Cyclizations;164
13.3;III. Total Synthesis of (-)-Steganone;169
13.4;IV. Total Synthesis of (+)-Isoschizandrin;180
13.5;V. Conclusion;192
13.6;References and Footnotes;193
14;CHAPTER 6. THE SYNTHESIS OF POLYCAVERNOSIDE A. AN EXAMPLE OF CONFORMATIONALLY GUIDED MACROLACTONIZATION;198
14.1;I. Introduction;198
14.2;II. Polycavernoside A: A Lethal Metabolite from Polycavernosa tsudai;200
14.3;III. First Generation Strategy;201
14.4;IV. Synthesis of a C10-C16 Dithiane Fragment;205
14.5;V. Intramolecular Alkoxy Carbonylation of 6-Hydroxy-l-octenes;208
14.6;VI. Synthesis of a C1-C9 Aldehyde Fragment and Failure of Dithiane Coupling;212
14.7;VII. A Revised Plan: Fragment Umpolung and an Antipodean Target;215
14.8;VIII. Fragment Union by a Nozaki-Hiyama-Kishi (NHK) Reaction;217
14.9;IX. The Quest for a Differentially Protected C10-C16 Aldehyde Fragment;221
14.10;X. Regioselective Macrolactonization of a Trihydroxy Carboxylic Acid;224
14.11;XI. Completion of Aglycon Core: A Formal Synthesis of Polycavernoside A;229
14.12;XII. Coup de Grace: The Realization of Polycavernoside A;231
14.13;XIII. Conclusion;232
14.14;References;233
15;CHAPTER 7. FIRST TOTAL SYNTHESIS OF SEVERAL NATURAL PRODUCTS BASED ON ALKYNE-Co2(CO)6 COMPLEXES;236
15.1;I. Introduction;236
15.2;II. First Total Synthesis of (+)-Secosyrins 1 and 2;237
15.3;III. First Total Synthesis of (-)-Ichthyothereol;248
15.4;IV. First Total Synthesis of (±)-8ß-Hydroxystreptazolone;254
15.5;V. Summary;267
15.6;References and Footnotes;267
16;CHAPTER 8. TOTAL SYNTHESIS OF MYRIAPORONES 1, 3, AND 4;271
16.1;I. The Foundation: Tedanolide and the Myriaporones;271
16.2;II. An Issue of Timing: A Strategy for the Synthesis of the Myriaporones;273
16.3;III. C9-C13: The Most Elegant Reaction is one That Works Well;275
16.4;IV. C8-C9: The Best Model System is the Natural Substrate;275
16.5;V. Deja Vu All Over Again: Evans Aldol Approach;278
16.6;VI. Hindsight is 20:20: Myriaporone 1 or Myriaporones 3 and 4;278
16.7;VII. A Critical Postponement: Late-Stage Epoxidation and the Targeting of Myriaporones 3 and 4;281
16.8;VIII. Unexpected Myriaporone 1 Formation;287
16.9;IX. Stereochemical Assignment of Myriaporones 1,3, and 4;290
16.10;X. Perspective;292
16.11;References and Footnotes;292
17;CHAPTER 9. ADVENTURES IN NATURAL PRODUCT SYNTHESIS: FROM DEEP SEA SPONGE TO PILOT PLANT. THE LARGE SCALE TOTAL SYNTHESIS OF THE MARINE NATURAL PRODUCT (+)-DISCODERMOLIDE;294
17.1;I. Introduction;294
17.2;II. Comments on the Structure;296
17.3;III. Project Background;297
17.4;IV. Literature Evaluation and Route Selection;299
17.5;V. Execution;307
17.6;VI. Synthesis Statistics;338
17.7;VII. Outlook;339
17.8;VIII. Conclusion and Summary;339
17.9;References and Footnotes;342
18;CHAPTER 10. SYNTHESIS OF APREPITANT;346
18.1;I. Introduction;346
18.2;II. Original Medicinal Chemistry Route and Process Research Evaluation;346
18.3;III. Oxazinone Synthesis;349
18.4;IV. Diastereoselective Acetal Formation and Olefin Hydrogenation;355
18.5;V. End Game and Triazolinone Synthesis;359
18.6;VI. Synthesis Revision;360
18.7;VII. 2nd Total Synthesis: Hofmann Elimination;362
18.8;VIII. 3r d Total Synthesis: Trans-Acetalization Reaction;364
18.9;IX. Chiral Alcohol Synthesis;368
18.10;X. 4th Total Synthesis: The Manufacturing Process - Discovery;369
18.11;XI. 4th Total Synthesis: The Manufacturing Process - Optimization;370
18.12;XII. Conclusion;374
18.13;References and Footnotes;375
19;CHAPTER 11. TOTAL SYNTHESIS AND MECHANISM OF ACTION STUDIES ON THE ANTITUMOR ALKALOID, (-)-AGELASTATIN A;377
19.1;I. Introduction: The Challenges Faced by Scientists Involved in 21st Century Genomics Research, and the Place of Synthetic Organic Chemistry in the Modern-Day Genomics Era;378
19.2;II. The Discovery of (-)-Agelastatin A and its Postulated Biogenesis;380
19.3;III. Initial Biological Screening of (-)-Agelastatin A;381
19.4;IV. Past Total Synthesis Studies on Agelastatin A;384
19.5;V. Our Reasons for Developing a New Total Synthesis of (-)-Agelastatin A;388
19.6;VI. Our Initial Retrosynthetic Plan;388
19.7;VII. Attempted Implementation of Our Initial Strategic Planning for (-)-Agelastatin A;390
19.8;VIII. A Second-Strike Strategy for (-)-Agelastatin A;398
19.9;IX. A Third-Strike Strategy for (-)-Agelastatin A: A Formal Total Synthesis;402
19.10;X. A New Endgame and Total Synthesis of (-)-Agelastatin A;406
19.11;XI. A Preliminary Comparison of the Antitumor Properties of (-)-Agelastatin A and Cisplatin Against Various Human Tumor Cell Lines;413
19.12;XII. Toxicological Studies on (-)-Agelastatin A;413
19.13;XIII. Preliminary Mechanism of Action Studies on (-)-Agelastatin A;414
19.14;XIV. Conclusions;415
19.15;References and Footnotes;416
20;CHAPTER 12. DESIGN AND SYNTHESIS OF COOPERATIVE "PINWHEEL" FLUORESCENT SENSORS;420
20.1;I. Introduction to Cooperative Recognition and Chemical Sensing;420
20.2;II. Synthesis of a Symmetrical Bis-trityl Mono-acetylene Sensor;422
20.3;III. Design of a Second Generation Fluorescent Pinwheel Sensor;427
20.4;IV. General Synthetic Strategy for Fluorescent Bis-trityl Sensors;429
20.5;V. Applications to a Dicarboxylate Sensor;433
20.6;VI. Applications to a Carbohydrate Sensor;433
20.7;VII. Conclusions;438
20.8;References and Footnotes;438
21;CHAPTER 13. FUNCTIONALIZATION OF PYRIDINES AND THIAZOLES VIA THE HALOGEN-DANCE REACTION, APPLICATION TO THE TOTAL SYNTHESIS OF CAERULOMYCIN C AND WS75624 B;440
21.1;I. Introduction;440
21.2;II. Pyridines - The Halogen-Dance Reaction;442
21.3;III. Retrosynthetic analysis;446
21.4;IV. Early Efforts, Limitations to the 1,3-Halogen-Dance Reaction;447
21.5;V. Successful 1,3- and 1,4-Halogen-Dance Reactions, Synthesis of the Core Pyridine Structure;449
21.6;VI. Completion of the Synthesis of Caerulomycin C;450
21.7;VII. Completion of the Synthesis of WS75624 B, Application of the Halogen-Dance reaction to Thiazoles;451
21.8;VIII. Conclusion;458
21.9;References and Footnotes;458
22;CHAPTER 14. DIASTEREOSELECTIVE INTRAMOLECULAR 4+3 CYCLOADDITION AND AN ENANTIOSELECTIVE TOTAL SYNTHESIS OF (+)-DACTYLOL;462
22.1;I. Introduction;462
22.2;II. Dactylol;463
22.3;III. 4+3 Cycloaddition Reactions of Cyclic Oxyallyl Zwitterions;466
22.4;IV. Synthesis of Cyclooctanoids via Intramolecular 4+3 Cycloaddition Reactions;469
22.5;V. Diastereocontrol in 4+3 Cycloaddition Reactions;473
22.6;VI. Retrosynthetic Analysis of (+)-Dactylol;474
22.7;VII. Preparation of the Diene Side Chain;475
22.8;VIII. Preparation of the Cycloaddition Substrate;478
22.9;IX. The Key 4+3 Cycloaddition Reaction;479
22.10;X. From the Cycloadduct to (+)-Dactylol;480
22.11;XI. Conclusion;487
22.12;References;487
23;INDEX;490