Enantio-reversal in Candida rugosa lipase-catalyzed esterification of 3-hydroxybutyric acid

Candida rugosa lipase (CRL)-catalyzed esterification of racemic 3-hydroxybutyric acid with different nucleophilic alcohols was studied. The alcohol chain length was found to have a profound role in the enantioselectivity of the reaction. As compared to the esterification with 1-butanol, use of longer alcohols surprisingly led to an enantio-reversal. Under optimized condition, the (R)-ester with 95–98% enantiomeric excess (ee) was obtained when the esterification was carried out with 1-hexanol and 1-octanol in the presence of freshly activated molecular sieve 4 Å.