Chiral drugs stereoselectivity

Manufacturing of chiral drugs has become increasingly important hrst to improve potency, second to improve yield, and third to extend the patent life for approved drugs based on racemic mixtures. Stereoselective synthetic methods are used to produce chiral drugs. There are three basic methods being applied ... 

It is estimated that approximately one-half of all drugs worldwide exist as stereoisomers. However, only one-half of stereoisomeric drugs are marketed as the individual stereoisomer and most of the latter are of natural or semi-synthetic origin. There is increasing awareness of the clinical importance of drug stereoselectivity because differences in the behavior of isomers in the chiral living system can result in significant differences in clinical outcomes. Table 1 presents a number of examples of these difference. 

R. N. Patel, Synthesis of Chiral Drug Intermediates, in R. N. Patel (Ed.), Stereoselective Biocatalysis, Marcel Dekker, New York, Basel, 2000, pp. 87-130. 

Even though it has been known for 100 years or more that stereoselectivity plays an important role in drug activity, chiral drugs have been developed and used as race-mates while neglecting the fact that they comprise mixtures of two or more compounds that may have quite different pharmacological properties [98,99]. An example with dramatic consequences is Thalidomide (2-(2,6-dioxo-3-piperidyl)isoindol-l,3-dion, Contergan). 

All of these methods have their own advantages and drawbacks. The aim of this chapter is to review the recent trends in the stereoselective synthesis of chiral drugs by presenting a restricted selection of relevant applications and results. Some of these have been chosen because they serve to illustrate the pro and cons of a certain approach rather than because of their own practical value. 

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