LIPASE-CATALYZED PRACTICAL SYNTHESIS OF (R)-1-BENZYL-3-HYDROXY-2,5-PYRROLIDINEDIONE AND ITS RELATED-COMPOUNDS

A practical method for preparing (R)-1-benzyl-3-hydroxy-2,5-pyrrolidin edione (1) was investigated by the use of the enzymatic hydrolysis of its acetate (2a). Among several hydrolases examined here, lipase PS fr om Pseudomonas cepacia gave the best result: In a mixed solvent (1:1 v /v) of dioxane and a phosphate buffer (pH 7), the hydrolysis took plac e smoothly with a high enantioselectivity (E > 3000). Several 3-alkano yl derivatives of 1 were subjected to the lipase PS-catalyzed hydrolys is. The chain length of the alkanoyl does not noticeably influence the reaction rate or the enantioselectivity. In contrast, the hydrolysis of the l-benzoyl derivative proceeded slowly with a low enantioselecti vity (E = 19). The syntheses of optically active 3-hydroxypyrrolidines and 3-hydroxypiperidines were also achieved under the reaction condit ions similar to the lipase PS-catalyzed hydrolysis of 2a.