Biocatalytic, Stereoselective Deuteration of α-Amino Acids and Methyl Esters

Abstract

α-2H Amino acids are valuable precursors toward labeled pharmaceutical agents and tools for studying biological systems; however, these molecules are costly to purchase and challenging to synthesize in a site- and stereoselective manner. Here, we show that an α-oxoamine synthase that evolved for saxitoxin biosynthesis, SxtA AONS, is capable of producing a range of α-2H amino acids and esters site- and stereoselectively using D2O as the deuterium source. Additionally, we demonstrate the utility of this operationally simple reaction on preparative-scale in the stereoselective chemoenzymatic synthesis of a deuterated analogue of safinamide, a drug used to treat Parkinson’s disease.