Categories: Organic Chemistry >> Synthesis, Bio >> Biocatalysis, Natural Products
The Way of Synthesis: Evolution of Design and Methods for Natural Products
Tomas Hudlický, Josephine W. Reed
Paperback, 1018 Pages
First Edition, 2007
This two-colored textbook presents not only synthetic ways to design organic compounds, it also contains a compilation of the most important total syntheses of the last 50 years with a comparative view of multiple designs for the same targets. It explains different tactics and strategies, making it easy to apply to many problems, regardless of the synthetic question in hand. Following a historical view of the evolution of synthesis, the book goes on to look at principles and issues impacting synthesis and design as well as principles and issues of methods. The sections on comparative design cover classics in terpenes and alkaloid synthesis, while a further section covers such miscellaneous syntheses as Maytansine, Palytoxin, Brevetoxin B and Indinavir. The whole is rounded off with a look at future perspectives and, what makes this textbook extraordinairy, with personal recollections of the chemists, who synthesized these fascinating compounds.
With its attractive layout highlighting key parts and tactics using a second color, this is a useful tool for organic chemists, lecturers and students in chemistry, as well as those working in the chemical industry.
The field of total synthesis has undergone a significant transformation over the past 60 years. Groundbreaking new methods such as “umpolung”, directed ortho-metalation and Pd-catalyzed cross-couplings have enabled the rapid and direct construction of natural products. New, more selective reactions help to dispense with protecting groups. Over this time, it has become possible to build strained cyclic compounds in just a few steps.
With “The Way of Synthesis: Evolution of Design and Methods for Natural Products”, Tomás Hudlický has produced a book that makes it possible to visualize the development over time of synthetic methods, strategies and tactics, wonderfully exemplified in a multitude of selected natural products. The introduction presents a number of important chemical transformations and strategies that have been successfully applied to the synthesis of many complex natural products. The reader here might expect a historical overview, and not such a detailed description of the reactions. In this introduction and in the subsequent total syntheses, we hear again and again from the researchers involved. In this way, the reader experiences the circumstances under which discoveries are made; this is truly fascinating, and paints an accurate portrait of accomplishments in the laboratory.
Likewise amazing are the candid words of the author himself, who does not shy away from speaking critically of the state of today’s science. Thus, enormous value is placed on the highest possible yields and enantioselectivity in publications, yet not infrequently these results are irreproducible. The pressure to publish genuinely groundbreaking, new, selective syntheses in high yield leads to a mindset where some of the stumbling blocks and dead ends are consigned to obscurity. Slight incremental improvements in a total synthesis can only enrich the literature when the target natural product has enormous commercial potential, but are otherwise not worth the effort of publication. As a researcher, one must also face pressure from the research sponsors and from one’s own institution.
The natural products presented in the book are treated in a historical context. Their discovery, structure elucidation and significance are all described within a few pages. The interesting part is the comparison of various tactics for assembling the corresponding skeleton, from which the advantages and disadvantages can readily be recognized, as well as the important intermediate steps and the differences between them. The presentation of these respective syntheses succeeds brilliantly! The author comes to the point succinctly, but with precision. Here again, the wealth of literature references and personal notes permit the subject matter to be dealt with in detail.
Hudlický has authored a very personal book, parts of which are simply fascinating to read. In contrast to Nicolaou’s "Classics in Total Synthesis", which includes some detailed explanations on intermediate steps, "The Way of Synthesis: Evolution of Design and Methods for Natural Products" offers a more truly holistic appraisal that even includes answers to philosophical questions. Advanced students who are pondering which field they should enter might just find answers here, as will those persons who are interested in the strategies and tactics of total synthesis. The book makes for a pleasurable read that will plant the seeds of new ideas in the reader’s mind, but it should not be viewed as purely a textbook. The reason is that it tends to stray too far afield in parts, a judgment for which the author can generously be forgiven.
Note added June 17th, 2020:
Some pictures of the book have later been reused in a controversial publication by Hudlicky in ANIE, that has been retracted. And this retraction is correct. However, the book has a different tone and you must take the decision by youself, whether you like to read a text, that somewhat glorifies the past. For sure, it is better to read the full context first (which is summarized by Derek Low here):
Part 1: Introduction.
Part 2: Strategy and Tactics.
Part 3: Comparative Design: classics in Terpene Synthesis.
Part 4: Comparative Design: Classics in Alkaloid Synthesis.
Part 5: Miscellaneous Compounds.
Part 6: Outlook.
Part 7: Acknowledgments.
Part 8: Appendix.
Index of personal recollection.