Enzyme-Catalyzed Hydrolysis of Bicycloheptane and Cyclobutene Diesters to Monoesters

Diacid formation is a major problem in the conventional chemical hydrolysis of a diester to a monoester. Enzyme-catalyzed hydrolysis of dimethyl bicyclo[2.2.1]heptane-1,4-dicarboxylate (1) by lipases from Candida antarctica and Burkholderia cepacia gave the corresponding monoester 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid (2) in excellent yields with negligible amounts of diacid 3. About 100 kg of monoester 2 was prepared in 78% yield by hydrolysis of diester 1 with a commercially available lipase from B. cepacia. A more efficient process for the hydrolysis of 1 that give monoester 2 in 82% yield was subsequently developed using significantly lower amounts of the commercially available immobilized lipase B from C. antarctica. The commercially available immobilized lipase B from C. antarctica and porcine liver esterase were also efficient for the selective hydrolysis of dimethyl cyclobut-1-ene-1,2-dicarboxylate (4) to the corresponding monoester 5 in yields of 78% and 87%, respectively.