Enantioselective lipase-catalyzed ester hydrolysis: effects on rates and enantioselectivity from a variation of the ester structure.

In order to make a preliminary study of substituent effects on the rate and enantioselectivity obtained in esterolytic reactions catalyzed by a lipase from Candida rugosa, a series of racemic esters, derived from some alpha-alkyl and alpha-halo phenylacetic acids, were prepared. The reactions were studied at pH 6.0 and 50 degrees C under which conditions uncatalyzed hydrolysis was relatively slow. Reaction samples were studied at different points of time by means of analytical chiral reversed-phase liquid chromatography, which permitted the simultaneous determination of product enantiomeric excess and of the degree of total ester hydrolysis. These data were then used to calculate initial rates as well as enantioselectivity. An increase of the steric bulk of the alpha-substituent was found to highly decrease the rate of the reaction. On the other hand, rates were higher for the p-nitrophenyl esters than for the corresponding 2-chloroethyl esters. Consistently, the enantioselectivity was found to be higher for the latter type of ester. The esters of the alpha-halo (bromo and chloro) phenylacetic acids gave mandelic acid as the final product. This was caused by a rapid solvolysis of the alpha-halo phenylacetic acid initially formed.