Investigation of the Impact of Water on the Enantioselectivity Displayed by CALB in the Kinetic Resolution of δ-Functionalized Alkan-2-ol Derivatives

It is shown that the low enantioselectivity of Candida antarctica lipase B (CALB)-catalyzed transesterification of a -functionalized alkan-2-ol to its acetate does not correlate at all with the high enantioselectivity of the CALB-catalyzed hydrolysis of the corresponding acetate in water. This lack of correlation is unusual and for unfunctionalized alkan-2-ol derivatives there is a very good correlation between the enantioselectivity of transesterification of the alcohol and hydrolysis of the corresponding acetate (E>200 in both cases). The results confirm previous predictions from molecular modeling. The water effect was mimicked by CALB variant Ala281Ser, which showed an enhanced enantioselectivity in transesterification of -functionalized alkan-2-ols compared to wild-type CALB.