An unexpected inversion of CAL-B enantiopreference based on substrate engineering of 2-bromoesters: Effect of (R)-1-phenylethyl moiety

Abstract

Candida antarctica lipase B (CAL-B) is one of the most useful enzymes for preparation of optically active alcohols and amines. However, CAL-B substrate’s scope for enzymatic kinetic resolution (EKR) of carboxylic acids and their derivatives is limited, especially by low stereoselectivity. In an attempt to overcome this drawback, we decided to employ substrate engineering of enzymatic transesterification of 2-bromobutyric esters by changing the alcohol moiety of the structure. The modifications in the substrate resulted mainly in alterations of the conversion rate, but the inclusion of a chiral alcohol moiety such as (R)-1-phenylethanol resulted in inversion of CAL-B enantiopreference. When esters containing ordinary achiral aliphatic alcohol moiety were used, CAL-B presented S-selectivity. This selectivity was unexpectedly changed to R when an ester containing (R)-1-phenylethyl alcohol moiety was introduced. The use of (R)-1-phenylethanol and its derivatives as nucleophiles in the EKR of the 2-bromobutyric esters also resulted in the inversion of enzymatic enantiopreference. This is the first time that CAL-B acyl enantiopreference has been switched by the chiral nature of the alcohol moiety.