Old Yellow Enzyme-mediated reduction of β-cyano-α,β-unsaturated esters for the synthesis of chiral building blocks: stereochemical analysis of the reaction

Abstract

Baker's yeast and Old Yellow Enzyme-mediated reduction of the carbon–carbon double bonds of β-cyano-α,β-unsaturated esters was investigated, in order to broaden the applicability of this kind of reaction in the field of preparative organic chemistry. The synthetic significance of the enantioselective reduction of these difunctionalised substrates was shown by considering the conversion of saturated chiral cyanoesters into γ²-amino acid derivatives for foldamer chemistry applications. The stereochemical outcome of the biotransformations was carefully analysed by means of deuterium labeling experiments. The results of this analysis were employed to rationalise the effects of substrate-control on the stereoselectivity of a certain class of ene-reductase-mediated reduction reactions. A simple model was developed to describe the structural prerequisites for the optimal arrangement of the substrates within the binding site of OYE1-3 enzymes.