Journal of Medicinal Chemistry, 2007, Vol. 50, No. 21 5243
Book ReViews Discrimination of Chiral Compounds Using NMR Spectroscopy. By Thomas J. Wenzel. John Wiley & Sons, Inc., Hoboken, NJ. 2007. xxii + 549 pp. 16 × 24 cm. ISBN 0471763527. $110.00.
Aminoglycoside Antibiotics: From Chemical Biology to Drug Discovery. Edited by Dev P. Arya. Wiley-Interscience, Hoboken, NJ. 2007. x + 319 pp. 16 × 24.5 cm. ISBN 978-0471-74302-6. $ 115.00.
This treatise on the theory and application of chiral methods based on NMR spectroscopy offers the research chemist a very comprehensive overview of the capabilities of NMR approaches in establishing optical purity, assigning absolute configuration, and investigating conformational preferences. Experimental strategies for chiral discrimination are clearly described and supported by nearly 1700 references, many of which are from the 2005-2006 period. The book is organized by classes of chiral NMR reagents rather than by the types of compounds being analyzed in order to avoid the problematic chemical classification of polyfunctional molecules. The concise narrative uses appropriate and plentiful stereostructures to illustrate chemical properties and spectroscopic findings.
This is a marvelous text containing 11 chapters and over 1000 references current through 2005-2006. Its tables, figures, and structures/pathways are clearly illustrated throughout, with a central core of 15 color plates complementing many of the chapters. Synthetic methodology is not covered.
The advantages, versatility, and limitations of both chiral derivatizing agents and chiral solvating agents are discussed in terms that will lead an investigator to candidate reagents for practical new applications. Cautionary notes are offered in cases where trends in chemical shifts provide only tentative assignment of absolute configuration or where spectroscopic anomalies can lead to spurious configurational assignment. Guidelines are given for threshold chemical shift differences necessary for reliable predications of chirality or where X-ray crystallography and molecular mechanics calculations may be appropriate to validate NMR interpretation. Mechanisms of chiral recognition are explored, and much consideration is given to energy barriers between conformers or atropisomers. The first chapters primarily describe the use of carboxylic acids, alcohols, and amines as chiral derivatizing and solvating reagents. The remaining chapters describe the virtually unlimited potential of host-guest complexation for enantiomeric discrimination, the exploitation of metal complexes, the intriguing use of liquid crystals, the utility of deuterated substrates, and solid-state NMR technologies. Within these chapters, database approaches are shown to have emerged for the assignment of stereochemistry to common structural motifs in complex natural products. High-throughput methods now allow thousands of samples per day to be analyzed by chiral NMR techniques with implications for combinatorial libraries. Further, fundamental aspects of noncovalent molecular interactions are examined with potential relevance to drug design and receptor interaction. Once the reader appreciates that the very limited index needs to be used in conjunction with the extensive table of contents, not in lieu of it, this book becomes a foremost literature resource for NMR-based enantiodiscrimination.
Chapter 1 is a concise, well-written history of the aminoglycoside antibiotics (AGAs) from streptomycin to AGAs of 2006. Almost a third of the text is Chapter 2, a very comprehensive review of the biochemistry and genetics of AGA-producing microbes. Extensive tables and figures clearly present data from several dozen producers. Included is a section on the possible genetic engineering of AGA pathways under the assumption that “the biological activities of the AGAs have not reached an optimum as yet”. Further investigations are bound to reveal more new therapeutic entities. Chapter 3 covers the classic AGA resistance categories of target modification, agent alteration, and altered transport. A particularly interesting section here deals with “resistance proof” AGAs, which the authors admit are likely fiction, but they then describe how they may be developed. Additional chapters discuss AGA binding, agent design, and RNA-AGA interactions, while others introduce the reader to metalloaminoglycosides (Cu(II) and Fe(II/III)), describe their relationships to AGA pharmacology and toxicity, and provide an excellent discussion on AGA’s adverse effects emphasizing ototoxicity. The chapter by Elson-Schwab and Tor describes research into AGA analogues with anti-HIV and other antiviral activity. This discussion was updated in proof by the authors to include selective 2007 references. The final chapter (Chapter 11) complements the overall drug discovery tone of the text by reviewing new research on a variety of novel targets for AGAs including A and B DNA, DNA-RNA hybrids, and DNA triple helix domains. This is a “must have” text for anyone involved in AGA teaching or research. No better comprehensive treatise exists in this reviewer’s opinion. For those who are looking for a new area of research that can have a profound impact on the public’s health, this text offers a wonderful place to begin. The editor and his collaborators are to be commended on their superb efforts in bringing this field to our attention. As Davies concluded in his Introduction, “the aminoglycosides are very much alive”!
Kennerly S. Patrick
Robert J. Krueger
Department of Pharmaceutical Sciences South Carolina College of Pharmacy Medical UniVersity of South Carolina Charleston, South Carolina 29425
Pharmaceutical Sciences Department College of Pharmacy Ferris State UniVersity Big Rapids, Michigan 49307
JM700974C
JM701010A
10.1021/jm700974c
10.1021/jm701010a
