Enzymatic reduction of halogenated aryl ketones in an aqueous micellar solution with enhanced catalytic performance

Abstract

Enzymatic synthesis of enantiopure chiral halogenated aryl alcohols by ketoreductases (KREDs) is emerging but still challenging, due to the low solubility and slow mass transfer in aqueous media. As an eco-friendly tool for this issue, amphiphilic micelles are attractive. Herein, KRED-catalyzed reduction of halogenated aryl ketones in a TPGS-750-M formed aqueous micellar solution was conducted, achieving the corresponding chiral alcohols with moderate to excellent yields of up to 99% and remarkable enantioselectivities of >99% ee under the optimal conditions. Notably, the performance strengthening mechanisms of micelles in this process are illustrated, in which the solubilization position of the substrate plays an essential role and the substrates solubilized in the palisade layer of the micelles exhibit the highest increases in conversion and enantioselectivity. These findings provide guidance for rational design of enzyme catalysis in aqueous micellar media.