Lipase-catalyzed kinetic resolutions of racemic β- and γ-thiolactones

Several racemic beta- and gamma-thiolactones were synthesized and kinetic resolutions of them were executed using lipases. While a lipase from Pseudomonas cepacia (PCL) showed the highest enantioselectivity for (S)-form, (> 99% ee(s) at 53% conversion, E > 100) in the kinetic resolution of racemic alpha-methyl-beta-propiothiolactone (rac-MPTL), it showed no hydrolysis activity in the kinetic resolution of alpha-benzyl-alpha-methyl-beta-propiothiolactone (rac-BMPTL), suggesting that the changes in the size of alkyl group from rac-MPTL to rac-BMPTL leads to lower hydrolysis activity and enantioselectivity. In contrast, racemic gamma-butyrothiolactones were hydrolyzed by several lipases with low enantioselectivity, whereas a lipase from Candida antarctica (CAL) showed moderate enantioselectivity for (S)-form (> 99% ee(s) at 76% conversion, E = 11) in the kinetic resolution of racemic alpha-methyl-gamma-butyrothiolactone (rac-MBTL). Computer-aided molecular modeling was also performed to investigate the enantioselectivites and activities of PCL toward beta-propiothiolactones. The computer modeling results suggest that the alkyl side chains of beta-propiothiolactones and gamma-butyrothiolactones interact with amino acid residues around hydrophobic crevice, which affects the activity of PCL. (c) 2006 Published by Elsevier B.V.