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Categories: Analytical Chemistry, Medicinal Chemistry, Organic Chemistry

Chirality in Drug Research

Eric Francotte, Wolfgang Lindner

Hardcover, 351 Pages
First Edition, 2006
ISBN: 3-527-31076-2


Divided into the three main sections of synthesis, analysis and drug development, this handbook covers all stages of the drug development process, including large-scale synthesis and purification of chirally pure pharmaceuticals.

The two editors from academia and a major pharmaceutical company have assembled an experienced, international team who provide first-hand practical advice and report previously unpublished data.

In the first section, the isolation of chiral drugs from natural sources, their production in enzymatic processes and the resolution of racemic mixtures in preparative chromatography are outlined in separate chapters. For the section on qualitative and quantitative analysis, enantioselective chromatographic methods are presented as well as optical methods and CE-MS, while the final section deals with the pharmacology, pharmacokinetics and metabolic aspects of chiral drugs, devoting whole chapters to stereoselective drug binding and modeling chiral drug-receptor interactions.

With its unique industry-relevant aspects, this is a must for medicinal and pharmaceutical chemists.

Editorial Review

One reason behind the trend for medications to contain an active drug in the most enantiomerically enriched form possible is the availability of better methods for enantioselective synthesis and characterization. However, a greater knowledge of the biology involved is far more significant, as exemplified in particular by the tragic thalidomide episode, and this has led to paradigm shifts both in the industry and on approval boards. The other enantiomer frequently amounts only to so much inactive dead weight, while a number of such enantiomers are responsible for side effects; only in a few cases have specific compositions of a racemate or an enantiomeric pair demonstrated a synergistic effect.

During the actual development process, the question invariably arises of which step and which method to choose for introducing enrichment. Thus racemates are produced by parallel synthesis for drug candidates - it makes sense to resolve the racemate for the initial animal studies, whereas an optimized, enantioselective synthesis is employed in the course of production. These steps go hand in hand, so that the initial experiences in optimization (method development for analysis, and for synthesis and purification) are transferred directly into the next stage of development.

The book “Chirality in Drug Research” explains in detail why enantiomers should be considered as completely different drugs as a matter of principle, and provides a good and easily understood survey of the most important methods used in industry for the manufacture and analysis of drugs. It is indeed difficult for a single book to cover all of the different stages of development, all the way from the milligram-scale up to tonnes, but the present work appears to have succeeded in this regard. This monograph is ideal in that it provides an overview of the methods and technologies currently in use, and refers the reader to cited literature for more in-depth study where necessary. It can facilitate collaborations between the individual work groups involved in development, since all of the important principles and options are introduced. This work’s interdisciplinary character is also a boon for advanced students, making it an interesting read for those who wish to gain a greater familiarity with this area. “Chirality in Drug Research” provides its readers with a comprehensive overview of the field, and offers a simultaneous, integrated exposure to the important methods for both synthesis and analysis.


1 Chiral Drugs from a Historical Point of View (Joseph Gal).
2 Stereoselective Synthesis of Drugs – An Industrial Perspective (Hans-Jürgen Federsel).
3 Aspects of Chirality in Natural Products Drug Discovery (Philipp Krastel, Frank Petersen, Silvio Roggo, Esther Schmitt, and Ansgar Schuffenhauer).
4 Biotransformation Methods for Preparing Chiral Drugs and Drug Intermediates (Michael Müller and Marcel Wubbolts).
5 Resolution of Chiral Drugs and Drug Intermediates by Crystallisation (Kazuhiko Saigo).
6 Isolation and Production of Optically Pure Drugs by Enantioselective Chromatography (Eric Francotte).
7 Stereoselective Chromatographic Methods for Drug Analysis (Norbert M. Maier and Wolfgang Lindner).
8 Capillary Electrophoresis Coupled to Mass Spectrometry for Chiral Drugs Analysis (Serge Rudaz and Jean-Luc Veuthey).
9 Powerful Chiral Molecular Tools for Preparation of Enantiopure Alcohols and Simultaneous Determination of Their Absolute Configurations by X-Ray Crystallography and/or 1H NMR Anisotropy Methods (Nobuyuki Harada).
10 Keywords in Chirality Modeling Molecular Modeling of Chirality – Software and Literature Research on Chirality in Modeling, Chirality in Docking, Chiral Ligand–Receptor Interaction and Symmetry (Gerd Folkers, Mine Yarim, and Pavel Pospisil).