The Industrial Synthesis of Pure Enantiomers

Abstract

The ever-increasing demand for more selective drugs, pesticides, etc, which are more targeted in their action, show less toxic side effects, and are more environmentally acceptable, is providing an important stimulus to companies to market these products as pure optical isomers. In reality, a chiral drug administered as a racemic mixture amounts to two separate drugs, each with different pharmacodynamics and pharmacokinetics, being given simultaneously. This increasing awareness of the importance of chirality in the context of biological activity has stimulated a growing demand for efficient methods for the industrial synthesis of optically active compounds.

The various methods for the synthesis of pure enantiomers, viz, use of the chiral pool, resolution of racemates via crystallization techniques, or enzymatic methods and catalytic asymmetric synthesis, are reviewed and compared. The advantages and limitations of the various methods are discussed, and particular emphasis is placed on new developments such as the use of enzymes in organic media and catalytic asymmetric synthesis using metal-Binap complexes.

Given the rapidly growing repetoire of cost-effective methods available, the industrial synthesis of most chiral pharmaceuticals in enantiomerically pure form is clearly an economically viable proposition.