CHEMOENZYMATIC ENANTIOSELECTIVE SYNTHESIS OF BACLOFEN

We report two different chemoenzymatic enantioselective syntheses of baclofen based on the distinction between enantiotopic ester groups in compounds bearing a prochiral centre. In the first approach, the key step is the highly stereoselective enzymatic hydrolysis of dimethyl 3-(4-chlorophenyl)glutarate by chymotrypsin in an aqueous medium. In the second approach, the key step is the enzyme-catalyzed esterification of 2-(4-chlorophenyl)-l,3-propanediol by acetic anhydride in the presence of a lipase in an organic medium.