Chemical Education Today edited by
Book & Media Reviews
Jeffrey Kovac University of Tennessee Knoxville, TN 37996-1600
Molecular Diversity and Combinatorial Chemistry: Principles and Applications (Tetrahedron Organic Chemistry Series) by Michael C. Pirrung Elsevier: Oxford, 2004. 188 pp. ISBN 0080444938 (cloth). $165; ISBN 0080445322 (paperback). $55 reviewed by R. David Crouch
This monograph is Volume 24 in the Tetrahedron Organic Chemistry Series and stems from a series of lectures and courses on combinatorial chemistry that the author has taught at Caltech, Duke, and the University of California– Irvine. The intent of the book is to provide an introduction to the vast and growing field of combinatorial chemistry. Naively, I expected a book describing examples of molecules and libraries that were prepared using the methods of solution and solid phase synthesis. But, as this book reveals, the field is far more complex both in the methods that are used and in the philosophy of the practitioners in the field. With 19 chapters spread over fewer than 180 pages, the author uses a series of brief chapters in a logical sequence to provide an illuminating overview of combinatorial chemistry. He begins by using a biological analogy to combinatorial chemistry in Chapter 1 that most advanced undergraduates should follow. Amino acids, the small molecules in this case, are combined in nature to form “libraries” of peptides and proteins that nature then “screens” for activity through selection processes. With this natural process as a model, the author introduces synthetic applications in Chapters 2 through 4, where conventional organic chemistry processes are applied in ways that will be new to many students and allow the synthesis of libraries of large molecules. Chapter 2 uses peptides as the target molecules and these serve as models for the introduction of principles and techniques such as split/couple/ mix, peptides-on-pins and one-bead/one-compound. Chapters 3 and 4 examine solid-phase organic synthesis. Chapters 5, 6, and 8 address the question: how do we know which possible compound is on a bead or in a vial or a well? While Chapter 8 examines extensions and applications of standard techniques such as magic angle spinning NMR and on-bead infrared spectroscopy, I suspect that Chapters 5 and 6 will capture the attention of students. Chapter 5 addresses Encoded Combinatorial Chemistry in which codes or identification tags are attached to scaffolds at the same time that the small molecules that make up the active product are added. And Chapter 6 describes “transponder” technology in which physically isolated vials contain unique products and each vial is tagged with radio frequency transmitter. Given the tech-savvy generation that we now teach, I imagine that students will find these techniques to be of particular interest. The author returns to synthetic chemistry in Chapters 7 and 9 through 11 with coverage of topics such as the synthesis of analogs of oligopetides, peptoids, and ureas; solu1154
Journal of Chemical Education
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tion phase organic synthesis including fluorous methods; and examples of multi-component synthesis such as the Ugi, Passerini, Bignelli, and Hantsch dihydropyridine syntheses. Chapters 12 through 17 reveal the centrality of chemistry in the natural sciences. In these chapters, the author takes the reader through a wide range of applications of principles presented earlier in the book. From the cheminformatics used in medicinal chemistry through the development of catalysts and new materials such as organic light-emitting diodes, the power of combinatorial chemistry is clearly demonstrated. The discussion almost appears to have come full circle in Chapters 16 and 17 when the topics of peptides and nucleic acids reemerge but this time the discussion centers on human manipulations of these biological molecules. For the synthetic organic chemist, Chapter 18 presents Ley’s synthesis of epibatidine, which uses solid-supported reagents as aids to purification; Waldmann’s synthesis of dysidolide that could be modified to allow for analog synthesis; and Curran’s fluorous-mediated synthesis of a large library of mappicine analogs. This is what I had expected to read at the outset. That I learned so much more about the field of combinatorial chemistry speaks to the monograph’s value. The author has written this book with the advanced undergraduate or beginning graduate student as the target audience, not scholars working in the field. He suggests that it could be used as the text for a one-quarter course. As someone who regularly teaches undergraduates, I would find it difficult to use this book as a stand-alone text for a semesterlong advanced course. The book is written with a level of detail that provides an introduction to each topic but does not expand on the topics. Indeed, the author seems to realize the need for supplemental readings by providing a list of “Additional Reading” at the end of each chapter and a more extensive list of texts, Web sites, and reviews at the end of the book. These lists fill out details that are not included in this monograph and allow instructors to tailor a course to their audience. A brief selection of problems is provided at the end of each chapter with the solutions located in the book’s appendix, but instructors will certainly want to supplement them with additional problems. At times, the author lapses into the lingo of molecular biology with discussions of germ lines and phages, which can make for difficult reading by those of us who are not wellversed in the field. But as the overlap of chemistry and biology increases, this is not a bad thing. It is certainly useful for our students to recognize the relationship of chemistry and molecular biology. This is a nice book that provides a good introduction to the field of combinatorial chemistry; it would serve as a good textbook for an advanced undergraduate course in the field. And it is probably a good addition to a library that serves a primarily undergraduate audience. R. David Crouch is in the Department of Chemistry, Dickinson College, Carlisle, PA 17013-2896; crouch@ dickinson.edu
Vol. 82 No. 8 August 2005
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