Asymmetric Synthesis of Optically Active Lactones from Cyclic Acid Anhydrides Using Lipase in Organic Solvents1)

Under heterogeneous conditions, a lipase (Amano P) catalyzed the asymmetric ring opening of 3-substituted glutaric anhydrides with 1-butanol in diisopropyl ether to afford the R mono esters, which were converted to the 3-substituted δ-lactones having 60~93%e.e. This process offered a practical means for preparing optically active 3-methyl-δ-valerolactone (93%e.e.) which is a useful chiral building block. The enzyme hydrolyzed the corresponding dimethyl esters to give the S mono esters in an aqueous medium. In both reactions, the pro R carbonyl group was preferentially attacked to yield pairs of enantiomers.