Book Review

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Organic Chemistry (3rd Edition)

P. Y. Bruice, Pearson Education, UK, , xxxvii + 1247 pp., price £35.99, ISBN 0-13-017858-6 Search PubMedOffering an insightful review of organic chemistry textbooks is a difficult task. The market for textbooks aimed at undergraduate organic chemistry students is fiercely competitive and a process of natural selection ensures that only the best survive. Individual institutions make a decision on which text to recommend to their students based on a number of sometimes mutually exclusive criteria such as breadth, brevity, visual appeal, price, clarity, multimedia content and so on. Consequently, there is currently available a range of excellent organic chemistry textbooks, sometimes with little obvious difference between them. Indeed, the task of selecting one book from several candidates has led some institutions to throw the question back in the laps of the students who will actually use the books and even here, no clear winner can be determined.¹ The present case, Organic Chemistry by Paula Y. Bruice, is also an excellent book and makes the task of choosing one from the many that much more difficult.

This text is, in many ways, everything an undergraduate text should be and it would serve students well throughout all levels of undergraduate teaching. The material is presented in logical order moving from structure and bonding through hydrocarbon stereochemistry and resonance, substitution/elimination, spectroscopy, aromaticity, carbonyl chemistry, bioorganic chemistry and a range of ‘special topics’. One question that could be raised relates to the inclusion of heterocyclic chemistry and pericyclic reactions as special topics, given their importance to the field in general. It might have been better to include these within the ‘core’ of the text and shuffle some of the more detailed discussion of bioorganic chemistry (to which some 220 pages are devoted) into the special topics area.

Throughout, an effort is made to present material in a sequence that discourages rote learning. The concept of synthetic design is introduced quite early, which allows students to begin to grasp the concept that organic chemists need to be able to think both synthetically and retrosynthetically. This approach, which demands that students begin to see molecules in terms of how they would be made, as well as how they would react, is to be commended. The language of the text is fluid and well crafted and explains difficult concepts clearly. One test for whether a book is up to the job is to read the section on spin–spin coupling in NMR. Bruice certainly does an excellent job here and eventually manages to just touch on the area of multidimensional NMR, spiced with a short section on magnetic resonance imaging. Another particularly appealing feature is the way in which faces and short profiles have been put to the names of such luminaries as Markovnikov, Wittig and Grignard. Many key concepts are given a contextual twist by the use of boxed materials. As one would expect for any modern textbook on organic chemistry, there are many pages of worked and unworked problems.

One of the most impressive features of this book is the depth of supporting material that is available for both teachers and students. Apart from the now (apparently obligatory) CD-ROM carrying additional material to help students grasp key issues and test their knowledge, there are also many online resources available for both students and instructors. One particularly appealing aspect of this book and one that raises the stakes in the multimedia area in general is the so-called ‘Companion Website’. This site has clearly been built to help grapple with the issue of increasingly demanding and large student cohorts. For students, it contains figures and Chime renderings of various molecules connected to each chapter, web-based multi-choice practice questions, tutorials and other features. Once attempted, practice questions can be submitted and assessed online and the results sent to teachers in a number of text formats by e-mail. This feature seems as though it would be most appropriate for checking that students had actually attempted the practice questions as part of a hurdle requirement. From the standpoint of assessment there would be nothing stopping students from iteratively improving their scores to 100% by cyclic use of the browser’s ‘Back’ button and the online assessment feature. For teachers, it offers a syllabus generation tool and readily available figures from the book that can be imported directly into electronic presentations. Readers are encouraged to examine many of these features for themselves through the book’s website (www.prenhall.com/bruice). One more feature that is available but was not explored in this review are the BlackBoard and WebCT course modules.

Teachers of undergraduate organic chemistry examine candidate texts against a range of criteria and this book, along with many others, more than fulfils a handsome number of these. While individual institutions place different emphasis on certain criteria, Bruice’s book is recommended for serious consideration based on a number of key indicators.

John Lambert
University of Melbourne, , Australia

Combinatorial Library Design and Evaluation

Arup K. Ghose and Vellarkad N. Viswanadhan, Marcel Dekker, US, , xv + 631 pp., price 195, ISBN 0-8247-0487-8 Search PubMedTraditionally, organic synthesis is a bespoke process with compounds made one at a time. This used to be compatible with the speed of drug discovery assays until the development of high-throughput screening by the pharmaceutical industry. The resulting bottleneck has fuelled the rapid and dramatic growth of combinatorial chemistry, leading to techniques that enable the synthesis of hundreds to thousands of compounds per day. Now that we can access such large collections of molecules, the question of which ones to make becomes even more critical. The editors have assembled a timely overview of the computational tools used in the design and evaluation of combinatorial libraries. This is an area of intense industrial effort currently, and many leading practitioners from both big pharma and smaller biotech companies have contributed to this monograph.

The book begins with an introductory chapter, ‘Library Design Concepts and Implementation Strategies’ by Doug Hobbs and Tao Guo. In only 40 pages, they have succeeded in providing an excellent snapshot of combinatorial organic synthesis illustrated with many well-chosen examples. The next section, ‘Design Principles’, consists of six chapters on general computational methods. Arup Ghose et al. discuss different approaches to pharmacophore modeling. The important area of quantitative structure–activity relationship (QSAR) in drug design is broadly reviewed by Asim Debnath, followed by a chapter on 3D QSAR by Gordon Crippen and Scott Wildman. Two computational approaches to ligand docking by Gennady Verkhivker et al. and Catherine Tenette-Souaille et al. deal with binding energy landscapes and fast continuum electrostatics respectively. The section concludes with an interesting chapter on integrating the prediction of pharmacokinetic properties with binding affinity by Tudor Oprea et al.

The profiling of libraries and evaluation of their ‘drugability’ forms the basis for the next set of chapters, ‘Current Methods and Software Tools’. Compounds from the Available Chemicals Directory (ACD) and the Comprehensive Medicinal Chemistry (CMC) database are grouped according to parameters such as log P and number of rotatable bonds in chapters by Vellarkad Viswanadhan et al. and Jens Sadowski. The enumeration of library diversity is a controversial topic without universal consensus, and the approach taken by Molecular Simulations in their Cerius2 software package is outlined by Robert Brown et al. A complementary chapter by Robert Clark from Tripos describes the Sybyl program, while Valerie Gillet and Peter Willett review algorithms for dissimilarity-based compound selection. Newer computational techniques are also covered in chapters by Alexander Tropsha on inverse QSAR, Andrew Good et al. on 3D pharmacophore-based library design, and Dragos Horvath on fuzzy logic.

The final section, ‘Applications’ shows how the above tools are employed in an industrial setting. Dona Schnur and Prabha Venkatarangan discuss cell-based diversity matrices. Structure-based combinatorial library design has proven to be a highly successful approach to drug discovery and is the subject of two chapters. Donatella Tondi and Maria Costi describe a series of literature examples on protease and thymidylate kinase inhibition, while Diane Joseph-McCarthy reviews the multiple copy simultaneous search method. The book ends with chapters on the application of genetic algorithms for lead generation by Jasbir Singh and Adi Treasurywala, and the design of libraries mimicking biological motifs by Hanoch Senderowitz and Rakefet Rosenfeld.

Overall, the book can be read as a series of stand-alone chapters and the editors have kept the degree of overlap between chapters to a reasonable level. The literature is covered up to 1999 with a few references from 2000. More care should have been taken in compiling the index. Although Lipinski's ‘Rule of Five’ is mentioned more than once, it is not listed as such. Other index terms are vaguely defined: topics like ‘Inhibitors’ and ‘Large Combinatorial Libraries’ are given only one page reference despite cropping up throughout the book.

This book will primarily appeal to those involved in either combinatorial synthesis or computational chemistry. Those in the first category that are curious about the software tools available and the rationale behind programs in routine use will profit from reading this book. Practising computational chemists might find much of the material here to be already familiar to them. Nevertheless, the book is a handy compilation of diverse computational methods and examples of drug discovery applications in a single reference source. Some of the chapters would also be useful as supplementary reading for advanced undergraduate courses in medicinal or computational chemistry.

A. Ganesan
University of Southampton, , UK

An Introduction to Medicinal Chemistry (2nd Edition)

Graham L. Patrick, Oxford University Press, Oxford, 2001, xxii + 622 pp., price £21.99, ISBN 0-19-850533 Search PubMedThis is the second edition of a useful introductory textbook on medicinal chemistry, the first edition of which appeared in 1995. This edition includes substantially more material than the first edition. The first part of the book contains chapters on cell structure, proteins, drug action on enzymes, drug action at receptors, receptor structure and signal transduction, and nucleic acids. These chapters are designed to give students a basis for the rationalization of drug action. In this general section there is perhaps a need to give students some idea of basic human biology, the circulatory, endocrine and nervous system and some idea of where the major diseases strike. There are then general chapters on drug development, drug design and pharmacokinetics. As with all the chapters, these are illustrated by a wealth of examples. Although there is only a brief general treatment of the pathways of drug metabolism at this stage, more is given in later chapters on specific compounds. There is a good section on pro-drugs which includes metabolic factors. There is then a chapter on quantitative structure–activity relationships and a description of the role of the various physicochemical parameters in establishing QSAR. A chapter on combinatorial synthesis then follows. Molecular modelling is then discussed. The final group of chapters are devoted to specific areas of medicinal chemistry. These include chapters on antibacterial agents, drugs which target the cholinergic and adrenergic systems, opium analgesics and the development of cimetidine as an example of rational drug design.

This is an interesting and useful book for undergraduates who are taking an option in medicinal chemistry. It is clearly written in a readable and sometimes amusing style including a number of cartoons. The examples that are used are drawn from modern drugs. Inevitably there has to be some selectivity in the examples and topics but this book does cover a wide area of medicinal chemistry. This book can be warmly recommended to students as an affordable introduction to medicinal chemistry.

J. R. Hanson
University of Sussex

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