Deracemisation of Mandelic Acid to Optically Pure Non-Natural L-Phenylglycine via a Redox-Neutral Biocatalytic Cascade

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 Dmandelic 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 (cc > 97%) at 94% conversion without the requirement of any additional redox reagents in stoichiometric amounts.