Resolution of Mandelic Acids by Lipase-Catalyzed Transesterifications in Organic Media

The resolution of mandelic acids was achieved via two types of lipase-catalyzed transesterifications in organic media, i.e., deacylation (alcoholysis) of O-acylated mandelates and acylation (transesterification) of mandelates. Through deacylation with butanol of methyl O-butyryl-(RS)-mandelates with or without a p-substituent, (S)-mandelates with 97% ee were produced at ca. 40% conversion (E 100) using Penicillium roqueforti lipase in isopropyl ether. Through acylation with vinyl acetate of methyl (RS)-mandelates, the free (R)-mandelates with 98% ee were obtained as recovered substrates at ca. 60% conversion (E 15) using Pseudomonas sp. lipase in the same solvent. According to the latter strategy, optically pure (> 99% ee) methyl (R)-mandelates were prepared on a gram scale. In the acylation reactions, vinyl esters carrying a shorter alkyl chain served as better acyl donors in terms of the conversion rate, while the enantioselectivity was the highest with vinyl butyrate. Additionally the stereochemical preference of the enzyme was inverted from S to R by using vinyl chloroacetate as the acyl donor.