Preparation of optically active 4-substituted γ-lactones by lipase-catalyzed optical resolution

Abstract

Optically active 4-substituted γ-lactones (3 and 4) were synthesized effectively using lipase-catalyzed optical resolution. N-methyl-4-hydroxyalkanamides (rac-1a-i) as substrates were prepared from N-methylsuccinimide. The alkylation of N-methylsuccinimide using Grignard reagents generated from various alkyl halides followed by reduction resulted in N-methyl-4-hydroxyalkanamides. The optical resolution of rac-1a-g was performed using Novozym 435-catalyzed stereoselective acetylation. The stereoselective preparation of 4-substituted γ-lactones (3 and 4) possessing various side chains such as isopentyl, phenyl, and phenethyl groups was achieved with more than 90% enantiopurity.