Lipase-catalyzed resolution of glycerol-based racemates

Enantioselectivity of six lipases toward the methanolysis of XOCH2CH(OCOR)C H2OCOR [X = trityl, 4-methoxytrityl or 4,4'-dimethoxytrityl and R = Me, Pr, or CH3(CH2)(8)] in diisopropyl ether was studied. The Pseudomonas lipases showed high enantioselectivity for the sn-1 position, leading to the unreac ted 2,3-di-O-acyl-1-O-X-sn-glycerol and the produced 2-O-acyl-3-O-X-sn-glyc erol. Substrates with R = Pr (ee 95% or higher for the two enantiomers at 5 0% conversion) were favored over shorter or longer chain eaters. A eerie am monium nitrate method allowed the removal of X. 4-Methoxytrityl as X led to the best result in terms of unchanged enantiopurity (ee 96%), short deprot ection time and only negligible 1,3-isomerization for the preparation of 2, 3-di-O-butyryl-sn-glycerol. The lipase-catalyzed acylation of 2-O-butyryl-3 -O-trityl-sn-glycerol with vinyl decanoate gave 2-O-butyryl-1-O-decanoyl-3- O-trityl-sn- glycerol. Interestingly, the two-step methanolysis of the subs trate (X = trityl, R = Pr) in the presence of Candida antarctica B lipase a llowed the preparation of highly enantiopure 3-O-tritylsn-glycerol (ee 94%) and enantiomerically enriched 2-O-butyryl-1-O-trityl-sn-glycerol, the init ially produced 2-monobutyrate being practically racemic. Chirality 11:432-4 39, 1999. (C) 1999 Wiley-Liss, Inc.