A new chemo-enzymatic route to chiral 2-hydroxy-4-phenylbutyrates by combining lactonase-mediated resolution with hydrogenation over Pd/C

摘要

A new chemo-enzymatic route to both isomers of 2-hydroxy-4-phenylbutyric acid is reported. The key step is the lactonase-catalyzed hydrolysis of cis- and trans-2-hydroxy-4-phenyl-4-butyrolactones followed by hydrogenation over Pd/C to afford optically pure 2-hydroxy-4-phenylbutyric acid.2-Hydroxy-4-phenylbutyrate is an important precursor to angiotensin-converting enzyme (ACE) inhibitors which have the (S)-homophenylalanine moiety as the central pharmaco-phore unit. These ACE inhibitors from the 'pril-family', such as Enalapril, Lisinopril, Cilapril and Benazepril, greatly expand the range of anti-hypertensive theurapeutics.