Lipase-catalyzed synthesis of (S)-naproxen ester prodrug by transesterification in organic solvents |
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Authors: | Shau-Wei Tsai Chin-Shain Tsai Chun-Sheng Chang |
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Institution: | (1) Department of Chemical Engineering, National Cheng Kung University, 70101 Tainan Taiwan, Republic of China |
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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. |
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Keywords: | Lipase enantioselective transesterification (S)-naproxen ester prodrugs |
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