Dimethyl sulfoxide as a co-solvent dramatically enhances the enantioselectivity in lipase-catalysed resolutions of 2-phenoxypropionic acyl derivatives

Abstract

We recently reported that the enantioselectivity for subtilisin-catalysed hydrolysis of ethyl 2-(4-substituted phenoxy)propionates in aqueous buffer is found to be dramatically enhanced by addition of dimethyl sulfoxide (DMSO). In our present work, as one of the useful methods for improving the enzyme’s enantioselectivity, this approach using DMSO is tested for both hydrolysis and transesterification catalysed by various lipases. For instance, for Candida rugosa lipase-catalysed hydrolysis in aqueous buffer containing DMSO, the optimum additive conditions (50–65 vol% DMSO) markedly enhance the enantioselectivity toward the substrates used, as compared with that for no-additive conditions, in spite of a decrease in the enzymatic activity. On the other hand, for Pseudomonas cepacia lipase-catalysed hydrolysis, the addition of DMSO to the reaction medium enhances the enantioselectivity with an increase in the enzymatic activity. Also, the DMSO effect on the enantioselectivity can apply to the lipase-catalysed transesterification in organic solvent. A mechanism for the DMSO-induced enhancement of the lipase’s enantioselectivity is briefly discussed on the basis of the values of the initial rates obtained for each enantiomer of the substrate used.