Screening for amidoxime reductases in plant roots and Saccharomyces cerevisiae - Development of biocatalytic method for chemoselective amidine synthesis

Abstract

The novel biocatalytic method for the synthesis of pharmaceutically relevant N-unsubstituted amidines was presented. The application of whole cells from commonly available vegetables allowed for the chemoselective reduction of the amidoxime moiety in the presence of other substituents prone to reduction or dehalogenation e.g. carbon-carbon double bond. Under optimized conditions several amidines were obtained with high yield up to 97% in aqueous medium at ambient temperature and atmospheric pressure. The practical potential of the newly developed method was shown in the preparative synthesis of anti-parasitic drug, phenamidine. Moreover, for the first time the enantioselective bioreduction of chiral racemic amidoximes to the corresponding amidines has been shown. The developed sustainable biocatalytic protocol fulfils the green chemistry rules and no application of metal catalysts meets the strict requirements of the pharmaceutical industry regarding metal contamination.

Keywords: Amidines; Biocatalysis; Bioreduction; Chemoselectivity; Oximes; Saccharomyces cerevisiae.