The mechanistic promiscuity of the enzymatic esterification of chiral carboxylic acids

The studies on the enzymatic kinetic resolution of 3-phenyl-4-pentenoic acid with various trialkyl orthoesters as alkoxy group donors are presented. The obtained results indicate that enantioselectivity of presented reaction is closely related to the alkoxy group donor structure. Based on critical analysis of the literature data and our own results we found that the previously recognized mechanism of such transformation is highly unlikely. In this paper we proposed a new revised mechanism explaining the role of alkoxy group donors. For trialkyl orthobenzoates excellent enzymatic kinetic resolution of target substrate was achieved. The presented method is an unique example of an enzymatic promiscuous activity toward esterification of carboxylic acids.