Deracemisation of Mandelic Acid to Optically Pure Non‐Natural <scp>L</scp>‐Phenylglycine <i>via</i> a Redox‐Neutral Biocatalytic Cascade

Abstract

Abstract A biocatalytic redox‐neutral reaction cascade was designed for the deracemisation of racemic mandelic acid to yield optically pure L ‐phenylglycine employing three enzymes. The cascade consisted of three steps: a racemisation, an enantioselective oxidation and a stereoselective reductive amination. The enantioselective oxidation of D ‐mandelic acid to the corresponding oxo acid was coupled with the stereoselective reductive amination of the latter; thus the oxidation as well as the reduction reactions were performed simultaneously. The formal hydrogen abstracted in the first step – the oxidation – was consumed in the reductive amination allowing a redox‐neutral cascade due to a cascade‐internal cofactor recycling. The enantiomers of the starting material were interconverted by a racemase (mandelate racemase) ensuring that in theory 100% of the starting material can be transformed. Using this set‐up racemic mandelic acid was transformed to optically pure L ‐phenylglycine ( ee &gt;97%) at 94% conversion without the requirement of any additional redox reagents in stoichiometric amounts.