CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

c) Kinetic resolution with biochemical and chemical protocols.
Another important strategy in the preparation of enantiomerically pure compounds
is the kinetic resolution of racemic substrates by enzymatic or chemical protocols. This
strategy is based on the fact that the enantiomeric compounds often show different reaction
rates under a given condition. Thus, by proper choice of the reagents/ conditions, a very
effective means of separating the enantiomers can, in principle, be obtained. Especially
enzymes are nowadays accepted as useful tools in organic synthesis as they catalyze many
reactions under very mild conditions, and show high reaction and enantio-selectivity as
well as substrate specificity. Because many important enzymes are readily available - for
example, esterases (CO 2 R → CO 2 H), amidases (CONHR → CO 2 H), hydrogenases (C=O
→ CHOH) and aldolases (RCHO → RCH(OH)CH 2 COR'), biocatalysis plays a significant
role in the development of asymmetric synthesis. 14a It is also possible to rationalize the
specificity of an enzyme-catalyzed reaction, when the enzyme’s active site structure is
known. In these cases, it is usually found that the enzyme binds the substrate via hydrogen
bonding, electrostatic or polarization forces or Van der Waals interactions. The enzymatic
reactions can be carried out in aqueous and organic media.
An offshoot in the age-old method for the preparation of enantiomerically pure
compounds is fermentation which is defined as the transformation mediated by growing
microorganisms under anaerobic conditions. Various speciality chemicals like the β-lactam
antibiotics, vitamins and other pharmaceutical compounds are mostly prepared by this
route. A major drawback of enzymatic and fermentation processes is that only one of the
two possible enantiomers can be prepared by these. Several reviews and books on the
application of biocatalysts in organic synthesis have appeared. 14a,b
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