One-pot chemoenzymatic synthesis of chiral 1,3-diols using an enantioselective aldol reaction with chiral Zn2+ complex catalysts and enzymatic reduction using oxidoreductases with cofactor regeneration

Abstract

We previously reported on enantioselective aldol reactions of acetone and some aldehydes catalyzed by chiral Zn(2+) complexes of L-prolyl-pendant [12]aneN(4) (L-ZnL(1)) and L-valyl-pendant [12]aneN(4) (L-ZnL(2)) in aqueous solution. Here, we report on the one-pot chemoenzymatic synthesis of chiral 1,3-diols in an aqueous solvent system at room temperature by a combination of enantioselective aldol reactions catalyzed by Zn(2+) complexes of L- and D-phenylalanyl-pendant [12]aneN(4) (L-ZnL(3) and D-ZnL(3) ) and the successive enantioselective reduction of the aldol products using oxidoreductases with the regeneration of the NADH (reduced form of nicotinamine adenine dinucleotide) cofactor. The findings indicate that all four stereoisomers of 1,3-diols can be produced by appropriate selection of a chiral Zn(2+)-complex and an oxidoreductase commercially available from the "Chiralscreen OH" kit.