Comparison of Chemical and Biochemical Reduction Methods for the Synthesis of (R)-2-Hydroxy-4-Phenylbutyric Acid

(R)-2-Hydroxy-4-phenylbutyric acid is a precursor for the production of Angiotensin Converting Enzyme (ACE) inhibitors. This paper describes its synthesis by enantioselective reduction of the corresponding α-ketoacid. Four approaches are described/compared: enzymatic reduction under catalysis of a NADH-dependent dehydrogenase that is performed in an enzyme membrane reactor including coenzyme regeneration and microbial transformation by means of Proteus vulgaris in a packed bed reactor. Furthermore, two chemical enantioselective hydrogenation methods are described: heterogeneous hydrogenation with a modified Platinum catalyst and homogeneous hydrogenation with a soluble chiral Rhodium diphosphine complex.