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Book Reviews Anti-AIDS Drug Development. Challenges, Strategies and Prospects. Edited by Prem Mohan and Masanori Babi. Harwood Academic Publishers, Switzerland. 1995. x + 298 pp. 18 × 25.5 cm. ISBN 3-7186-5698-1. $85.00. The editors of this volume have put together a wellorganized treatise with 12 chapters covering the major topics of interest in the field of anti-HIV chemotherapeutic agents. References are numerous through 1993, but more recent research is not included. Therefore, this book is useful to the researcher or student who desires historical perspective. The first chapter, written by E. De Clercq, introduces the book by describing potential targets in the life cycle of HIV suitable for therapeutic intervention. A chapter summarizing the work in the prolific field of nucleotide reverse transcriptase inhibitors, written in the style of an Annual Reports in Medicinal Chemistry review, follows. It is difficult to gain an overview of this field and where it is headed from this chapter, although it contains a good section on 3′-heteroatom-substituted nucleosides such as 3TC. The mechanism of action and potential value of imino sugar R-glucosidase inhibitors is discussed in a well-written and easily understood chapter. The chapter on the inhibition of HIV protease is well written and provides a good account of the rationale and development of peptide-based protease inhibitors. Notably absent is recent work disclosed in 1994 which describes the discovery of potent nonpeptide-based HIV protease inhibitors. Seven major class of HIV-1 specific reverse transcriptase inhibitors are covered in a chapter which focuses on structureactivity relationships, mechanism of inhibition, nature of viral resistance development, pharmaceutical profiles, and results of clinical studies. An error in the chemical structure of the BHAPs detracted from this particular reviewer’s enjoyment of this chapter. One very useful chapter for the medicinal chemist conducting research in this field is entitled “Anti-HIV Drug Test Systems: Significance and Limitations”. This chapter describes the factors that affect antiviral test results such as the nature of the target cells, components of the culture medium, and timing of drug addition. It also describes current approaches toward measurement of surrogate markers in the clinical setting. Other chapters include discussions of resistance, regulatory proteins, CD4 mimetics, antisense oligonucleotides, plant-derived anti-HIV compounds, and polyanionic anti-HIV compounds. Overall, this book does a good job of detailing therapeutic targets and discussing progress toward developing effective anti-AIDS drugs. Unfortunately the book is slightly out of date, and thus discussions describing recent clinical experiences suffer. Nevertheless, this book is a good investment for the medicinal chemist
interested in learning about a variety of approaches to developing anti-HIV therapeutics. Donna L. Romero Pharmacia & Upjohn, Inc. Medicinal Chemistry Research 301 Henrietta Street Kalamazoo, Michigan 49001 JM960104D
Modern Conformational Analysis: Elucidating Novel Exciting Molecular Structures. By Helena Dodziuk. VCH Publishers, Inc., New York. 1995. xii + 264 pp. 16 × 24 cm. ISBN 1-56081-689-9. $99.95. Despite one’s initial impression on reading the title, this book is not a text on conformational analysis. A more apt description of the contents of this work, which is a recent contribution to the VCH series Methods in Stereochemical Analysis, would dispense with the first three words of the title. The focus of this book is explained in the preface wherein the author writes, “I am fascinated by the beauty and variety of molecular shapes. To present some of them and to convey some of my fascination to the readers are the main aims of the book.” Indeed, this book is a well-written, interesting overview of unusual molecular architecture and topology with recent references to the primary literature, but the reader searching for a monograph covering topics in classical conformational analysis would be well advised to look elsewhere. The book is divided into 12 chapters, which, as noted by the author, “are written as separate entitites”, that may be read as independent reviews of each particular area. A short introduction (chapter 1, 22 pp) is followed by chapters entitled (2) Physical Methods as a Source of Information on the Spatial Structure of Organic Molecules (54 pp), (3) Theoretical Calculations as a Powerful Method of Structure Determination (22 pp), (4) Molecular Symmetry (20 pp), (5) Chirality (16 pp), (6) A Short Overview of Standard Structures of Organic Molecules (22 pp), (7) Potpourri of Saturated Pathologies (24 pp), (8) Molecules with Nonstandard Multiple Bonds and Aromatic Rings (22 pp), (9) New Topological Molecules, Starburst Dendrimers, and More (10 pp), (10) Complexes with Cyclodextrins and Other Examples of Self-Assembling Objects (22 pp), (11) Molecular Modeling (8 pp), and (12) Present and Future Applications (16 pp). The organization within each self-contained chapter is logical and well illustrated. A limitation of this work is the indexing: there is no author index, and the rather limited subject index does not contain all of the molecules discussed in the body of the book. The author has certainly met the major aim of the book as set out in the preface: this is a fascinating account of “the beauty and variety of molecular shapes” found in “organic molecules with unusual spatial structure”. As such it makes for a good read. The reader
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will, however, find little discussion of the principles of modern conformational analysis.
carbons) and/or shape (cyclic versus acyclic) of a symmetrical building block, with a last chapter specifically devoted to variously sized symmetric heterocycles as building blocks. The author has taken great pains to assemble as complete a listing of known syntheses, which utilize such building blocks, as possible, and the literature cited includes reports up to 1995. As an example of the book’s organization, chapter four, which discusses four-carbon chain building blocks, covers such subjects as the use of tartaric acid and derivatives (C2 symmetric) and succinic acid and derivatives as starting materials in a variety of syntheses. Chapter seven, on six-membered ring symmetric starting materials, is the longest chapter (fully one-fourth of the entire book), as it encompasses the extensive synthetic literature which has used such important cyclic six-membered symmetric starting materials as 4-substituted cyclohexanones, 1,3cyclohexanediones, quinones, and symmetrically substituted benzenes. The majority of the syntheses discussed throughout the book involves processes by which a symmetric starting material is converted into an asymmetric product because relatively few syntheses of symmetric molecules from symmetric starting materials have been reported. The use of enzymes to convert meso compounds into various asymmetric productssone of the more obvious examples of a synthetic method which utilizes symmetric molecules for the syntheses of asymmetric moleculessis given good coverage throughout the book, but readers will be surprised at the number and variety of other methods which exist for converting symmetric intermediates into useful asymmetric molecules! In summary, the author has written a comprehensive account of synthesis of symmetric molecules and syntheses which utilize symmetric molecules. While the book is accurately written, very timely, and relatively error-free, it would be more readable if one or two introductory paragraphs in each chapter were included to state an overview of that chapter’s contents. This book will probably not find use as a reference volume because the information which it contains is not easily retrievable unless one is searching, for example, for specific information pertaining to the use of a particular symmetric starting material in synthesis or information on the synthesis of a particular symmetric molecule. However, the book is a good discourse on contemporary organic synthesis, and it could be used as an auxiliary text in an advanced course on organic synthesis. It is not recommended as a “must buy” for personal libraries, but it is recommended for inclusion in institutional libraries which serve organic and medicinal chemists.
William F. Bailey Department of Chemistry University of Connecticut 216 Glenbrook Road U-60, Room 151 Storrs, Connecticut 06269-3060 JM9601056
Symmetry: A Basis for Synthesis Design. By TseLok Ho. John Wiley & Sons, Inc., New York. 1995. xv + 561 pp. 16.5 × 24 cm. ISBN 0-471-57376-0. $69.95. This book offers an up-to-date review of the syntheses of symmetric organic molecules and the usage of symmetric molecules as starting materials for the syntheses of larger organic molecules (symmetric or asymmetric). To some extent, it can be viewed as a contemporary overview of organic synthesissit is that comprehensivesbut the underlying theme throughout the work is that either the target molecule or a starting material/intermediate in the synthesis being discussed will be symmetric. As evident by the size of the book, a surprising number of synthetic routes, to large or small molecules, possess such a feature, and it is the author’s intent, as stated in the preface, to thus “inspire readers with the magnificence and relevance of symmetry to chemical synthesis”. His well-researched and clearly presented book accomplishes that aim. The book is organized into nine chapters. The first chapter is an introduction which defines, with numerous examples, symmetry elements and operations and then discusses various synthetic strategy principles relating to symmetry (e.g., symmetrization, desymmetrization, pseudosymmetry, and local symmetry) and asymmetric synthesis (e.g., enantiodivergence and enantioconvergence). This chapter could stand alone as a review of symmetry, stereochemistry, and asymmetric synthesis principles typically taught in graduate level advanced organic chemistry courses. The second chapter reviews known syntheses of symmetric molecules, from nonnatural compounds such as dodecahedrane and cubane to various natural products, the latter including highsymmetry natural products composed of asymmetric units. (With respect to the latter, it is interesting that the author overlooked nonactin, a classic example of a highly symmetric natural product composed of asymmetric subunits.) As with the first chapter, the second chapter of the book could stand alone as a useful and up-to-date review of the synthesis of natural and unnatural symmetric molecules. The remaining chapters of the book discuss the use of symmetric molecules as building blocks in synthesis. Each chapter is devoted to a certain size (number of
Robert D. Walkup Department of Chemistry & Biochemistry Texas Tech University Lubbock, Texas 79409-1061 JM960108I
