Classics in Total Synthesis III

K.C. Nicolaou holds joint appointments at The Scripps Research Institute, where he is the Chairman of the Department of Chemistry and holds the Darlene Shiley Chair in Chemistry and the Aline W. and L.S. Skaggs Professorship of Chemical Biology, and the University of California, San Diego, where he is Distinguished Professor of Chemistry. His impact on chemistry, biology and medicine flows from his research works in chemical synthesis and chemical biology described in numerous publications and patens. For his contributions to science and education, he was elected Fellow of the New York Academy of Sciences, Fellow of the American Academy of Arts and Sciences, Member of the National Academy of Sciences, USA, Member of the German Academy of Sciences Leopoldina, and Corresponding Member of the Academy of Athens, Greece. He is the recipient of many prizes, awards and honors. Jason S. Chen received his A.B. and A.M. degrees in Chemistry from Harvard University in 2001. After two years as a medicinal chemist at Enanta Pharmaceuticals, he began graduate studies at The Scripps Research Institute under the guidance of Professor K.C. Nicolaou. He received a National Defense Science and Engineering Graduate fellowship, and completed his Ph.D. studies in 2008. He currently is a post-doctoral fellow in Professor Nicolaou's laboratory.

INTRODUCTION: THE ADVANCING FIELD OF TOTAL SYNTHESIS
Targets
Strategies and Methods
Classics in Total Synthesis III

TETRODOTOXIN
Introduction
Kishi's Retrosynthetic Analysis and Strategy
Kishi's Total Synthesis
Du Bois' Retrosynthetic Analysis and Strategy
Du Bois' Total Synthesis
Conclusion

DISCODERMOLIDE
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

AZASPIRACID-1
Introduction
Nicolaou's Retrosynthetic Analysis and Strategy
Nicolaou's Total Synthesis
Evans' Retrosynthetic Analysis and Strategy
Evans' Total Synthesis
Conclusion

THIOSTREPTON
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

PENTACYCLOANAMMOXIC ACID METHYL ESTER
Introduction
First-Generation Retrosynthetic Analysis and Strategy
First-Generation Total Synthesis
Second-Generation Retrosynthetic Analysis and Strategy
Second-Generation Total Synthesis
Conclusion

LITTORALISONE, OSELTAMIVIR (TAMIFLU®), AND HIRSUTELLONE B
Introduction
Introduction to Littoralisone
Total Synthesis of Littoralisone
Introduction to Oseltamivir (Tamiflu®)
Total Synthesis of Oseltamivir (Tamiflu®)
Introduction to Hirsutellone B
Total Synthesis of Hirsutellone B
Conclusion

RUBICORDIFOLIN AND RUBIONCOLIN B
Introduction
Retrosynthetic Analysis of Rubicordifolin
Total Synthesis of Rubicordifolin
Retrosyntheticd Analysis of Rubioncolin B
Total Synthesis of Rubioncolin B
Conclusion

CYANTHIWIGINS U AND F
Introduction
Phillips' Retrosynthetic Analysis and Strategy
Phillips' Total Synthesis
Stolz' Retrosynthetic Analysis and Strategy
Stoltz' Total Synthesis
Conclusion

STEPHACIDIN B
Introduction
Myers' Retrosynthetic Analysis and Strategy
Meyers' Total Synthesis
Baran's Retrosynthetic Analysis and Strategy
Baran's Total Synthesis
Williams' Retrosynthetic Analysis and Strategy
Williams' Total Synthesis
Conclusion

ABYSSOMICIN C AND ATROP-ABYSSOMICIN C
Introduction
Sorensen's Retrosynthetic Analysis and Strategy
Sorensen's Total Synthesis of Abyssomicin C
Nicolaou's Retrosynthetic Analysis and Strategy
Nicolaou's Total Synthesis of Abyssomicin C and atrop-Abyssomicin C
Conclusion

TETRACYCLINE
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

BISANTHRAQUINONE NATURAL PRODUCTS
Introduction
Retrosynthetic Analysis and Strategy Toward 2,2'-epi-Cytoskyrin A, Rugulosin, and Rugulin
Total Synthesis of 2,2'-epi-Cytoskyrin A, Rugulosin, and Rugulin
Retrosynthetic Analysis and Strategy Toward Antibiotic BE-43472B
Total Synthesis of Antibiotic BE-43472B
Conclusion

GARSUBELLIN A
Introduction
Sibasaki and Kanai's Retrosynthetic Analysis and Strategy
Shibasaki and Kanai's Total Synthesis
Danishefsky's Retrosynthetic Analysis and Strategy
Danishefsky's Total Synthesis
Conclusion

WELWITINDOLINONE A
Introduction
Baran's Retrosynthetic Analysis and Strategy
Barans' Total Synthesis
Wood's Retrosynthetic Analysis and Strategy
Wood's Total Synthesis
Conclusion

IEJIMALIDE B
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

KEDARCIDIN CHROMOPHORE AND MADUROPEPTIN CHROMOPHORE
Introduction
Retrosynthetic Analysis and Strategy for Kedarcidin Chromophore
Total Synthesis of Kedarcidin Chromophore
Retrosynthetic Analysis and Strategy for Maduropeptin Chromophore
Total Synthesis of Maduropeptin Chromophore
Conclusion

BIYOUYANAGIN A
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

AZADIRACHTIN
Introduction
Retrosynthetic Analysis and Strategy
Synthesis
Conclusion

RESVERATROL-DERIVED NATURAL PRODUCTS
Introduction
Snyder's Retrosynthetic Analysis and Strategy for a Collection of Resveratrol-Derived Natural Products
Snyder's Total Synthesis of a Collection of Resveratrol-Derived Natural Products
Nicolaou and Chen's Retrosynthetic Analysis and Strategy for Hopeahainol A and Hopeanol
Nicolaou and Chen's Total Synthesis of Hopeahainol A and Hopeanol
Conclusion

CHLOROSULFOLIPID CYTOTOXIN
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

SPOROLIDE B
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

11,11'-DIDEOXYVERTICILLIN A AND CHAETOCIN
Introduction
Retrosynthetic Analysis and Strategy for 11,11'-Dideoxyverticillin A
Total Synthesis of 11,11'-Dideoxyverticillin A
Retrosynthetic Analysis and Strategy for Chaetocin
Total Synthesis of Chaetocin
Conclusion

VANNUSAL B
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

HAPLOPHYTINE
Introduction
Fukuyama and Tokuyama's Retrosynthetic Analysis and Strategy
Fukuyama and Tokuyama's Total Synthesis
Nicolaou and Chen's Retrosynthetic Analysis and Strategy
Nicolaou and Chen's Total Synthesis
Conclusion

PALAU'AMINE
Introduction
Retrosynthetic Analysis and Strategy
Total Synthesis
Conclusion

Nowadays, books that concentrate on the area of organic synthesis are numerous enough to fill whole inventories of libraries. But of that multitude, only a few books have been as outstanding in recent years as the series Classics in Total Synthesis, written by K. C. Nicolaou with various co-authors. This series can therefore already be justifiably called a classic in itself. Likewise, the third volume of this series, published by Wiley-VCH in February 2011, will surely continue the success of the previous volumes, and will certainly be a must-have in the libraries of synthetically orientated groups.
The concept of the preceding volumes has been closely retained. In 26 chapters, including an introductory chapter, syntheses of more than 40 natural products or natural product core structures are discussed in detail. The syntheses, together with historical excursions, have been taken from literature of the years 2003 to 2010. Each chapter begins with background information about the discovery, structure elucidation, and biological significance of the target molecule(s). To aid the reader_s orientation, key concepts of the total synthesis described are provided at the beginning of each chapter. After describing retrosyntheses that have been achieved, and any preliminary synthetic work, the chapter gives a very detailed description of the synthesis of the target structure, including almost all the individual steps. All literature references are clearly identified by chapter endnotes, thus allowing rapid access to the primary sources. The chapter ends with a short summary and a well-chosen, detailed, and extensive list of references. This alone is one of the great strengths of the book, and provides every synthetic chemist with an excellent pool for the solution of his or her own synthetic problems. Also particularly valuable for the reader are the short reviews on specific topics, which have the scope and style of review articles. Thus, one finds surveys on current topics of interest such as organocatalysis (Chapter 7: littoralisone, oseltamivir, hirsutellone B) and C_H activation (Chapter 2: tetrodotoxin) next to overviews of more classical themes such as Schenk ene reactions with singlet oxygen (Chapter 12: tetracycline), photochemically induced [2+2] cycloadditions (Chapter 18: biyouyanagin A), [2+2+2] cycloadditions, Diels-Alder reactions with o-quinones (Chapter 22: sporolid B), and Kagan-Molander SmI2 couplings (Chapter 24: vannusal B). The review of asymmetric halogenation reactions (Chapter 21: chlorosulfolipid cytotoxin) is particularly well-written, as it clearly demonstrates, to the young scientist as well as to the post- or pre-graduate student, that there are still enough chemical transformations that have not yet been sufficiently studied, and therefore leave room for personal creativity and ambition.
Novelties of this third volume compared to the previous ones are mainly concerned with the detailed contents. The depth of mechanistic discussions has been greatly increased. The introductions to the chapters often feature insights into the biosynthesis of the natural product concerned (e.g., Chapter 10: stephacidin). Some small sections describe problems associated with structure elucidation, which then led to revision of the supposed structure in the context of the total synthesis (e.g., in Chapter 4: azaspiracid-1). The very instructive concept of discussing and comparing several different syntheses of a target structure in a parallel fashion, which was introduced in the second volume of this series, has now been further developed in a clever way. Sometimes it would also have been useful for the synthetic chemist reader to be given an explanation of why a specific unusual reagent was chosen at a certain stage during the planning or carrying out of a synthesis, and why an apparently more convenient and conventional procedure was avoided. Such explanations, and possibly also descriptions of unsuccessful attempted routes, could give the reader an even more detailed insight into problems of reactivity or selectivity of a specific reagent or substrate.
The layout of this book has only been slightly changed compared with previous volumes. One innovation is the introduction of a colored title page at the beginning of each chapter, presenting an attractive graphical illustration of the target structure, together with its natural source and a picture of the leader of the group that worked on the total synthesis. However, the opportunity to similarly illustrate other parts of the chapter has not been taken; especially in the introduction, figures or graphics in color might have improved the accessibility of the contents. The question of whether it would be an advantage to also introduce color into the synthetic schemes depends on the reader_s personal taste as well as the costs of the book. On the other hand, the great success of this series does support a continuation of the style in its present form.
As the selection of synthetic target molecules for this book is exclusively taken from the more recent literature, in contrast to the first volume of the series, it remains to be seen whether the syntheses described will eventually become true classics. This book will certainly contribute its share to ensuring that these syntheses will be used as outstanding models for teaching and research purposes, even 20 or more years from now. One could also consider an even broader selection of target molecules and structures, which might be less close to the main author_s field of work and experience (at least 10 out of 26 chapters deal with the author_s syntheses). Indisputably, K. C. Nicolaou has made outstanding contributions in his research field. But who would not, for this very reason, like to see discussions of other scientists_ syntheses by the master himself?
A particularly extensive account is given in Chapter 3, which describes an impressive 60 g total synthesis of discodermolide by Novartis. This clearly demonstrates the increasing scientific, but also industrial, importance of complex syntheses of natural products. The present volume - and hopefully future books of this series - offer an exciting and outstanding overview of the subject of natural products total syntheses in its complexity and variety. Classics in Total Synthesis III will surely itself become a classic in the literature on the state of the art of contemporary organic synthetic chemistry.
Dirk Menche, Sebastian Essig
Organisch-Chemisches Institut
Ruprecht-Karls-Universität Heidelberg (Germany)
Angew. Chem. Int. Ed. 2011, 50, 5995 - 5996

?The present volume?and hopefully future books of this series?offer an exciting and outstanding overview of the subject of natural products total syntheses in its complexity and variety. Classics in Total Synthesis III will surely itself become a classic in the literature on the state of the art of contemporary organic synthetic chemistry.? ? Angewandte Chemie Int. Ed. 2011

"... a volume, (...) which any chemist with an interest in synthetic organic chemistry will wish to acquire." ?JACS (on a previous volume)

"...this superb book (...) will be an essential purchase for many organic chemists." ?Nature (on a previous volume)

"... One of my co-workers confessed that Classics I was the book on his bedside table while he prepared his thesis defense. Isn't that the highest distinction for a monograph?" ?Angewandte Chemie, 2004 (on a previous volume)