Lipase-catalyzed synthesis of (S)-naproxen ester prodrug by transesterification in organic solvents

Author： Tsai Shau-Wei Tsai Chin-Shain Chang Chun-Sheng

ISSN： 0273-2289

Source： Applied Biochemistry and Biotechnology, Vol.80, Iss.3, 1999-06, pp. : 205-219

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Abstract

A lipase-catalyzed enantioselective transesterification process was developed for the synthesis of (S)-naproxen 2-N-morpholinoethyl ester prodrug from racemic 2,2,2-trifluoroethyl naproxen ester in organic solvents. By selecting isooctane and 37°C as the best solvent and temperature, the apparent fits of the initial conversion rates for transesterification and hydrolysis side reaction suggest a ping-pong Bi-Bi enzymatic mechanism with the alcohol as a competitive enzyme inhibitor. Improvements in the initial conversion rate and the productivity for the desired (S)-ester product were obtained after comparing with the result of an enantioselective esterification process. Studies of water content in isooctane and alcohol containing various N,N-dialkylamino groups on the enzyme activity and enantioselectivity, as well as the recovery of (S)-ester product by using extraction, were also reported.