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

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