Enhancement of enantioselectivity in lipase-catalyzed resolution of N-(2-ethyl-6-methylphenyl)alanine by additives

Abstract

The lipase B from Candida antarctica (CAL-B)-catalyzed the enantioselective resolution of N-(2-ethyl-6-methylphenyl)alanine from the corresponding racemic methyl ester is investigated. However, the enantioselectivity of CAL-B towards the resolution is not high enough to obtain enantiomerically pure compound. With the aim to improve the enantioselectivity of enzyme, various additives including macrocyclic dioxotetraamines, organic compounds and ionic liquids are tested in the CAL-B-catalyzed hydrolysis. Under the optimized conditions, the highest enantioselectivity of CAL-B ( E > 100) is achieved in diethyl ether/water (15%, v/v), which is about 9.7-fold more enantioselective than that in pure buffered aqueous solution ( E = 12.1). When the macrocylic dioxotetraamine ( n-C 6H 13-MDTA) is added in the reaction medium, both catalytic activity and enantioselectivity of CAL-B are markedly enhanced ( E-value is up to 87.6 at 45.6% conversion only in 1.5 h). While the E-value is improved only up to 44.7 using ionic liquid ([ETOMG]BF 4) as additive, it can establish the green environment of enzymatic catalysis.