Lipase-catalyzed synthesis of (S)-naproxen ester prodrug by transesterification in organic solvents
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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.
Index EntriesLipase enantioselective transesterification (S)-naproxen ester prodrugs
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- 1.Federsel, H. J. (1993), CHEMTECH 12, 24–33.Google Scholar
- 3.Hutt, A. J. and Caldwell, J. (1984), Clin. Pharmacokinet. 9, 371–373.Google Scholar
- 5.Bundgaard, H. (1985), Design of Prodrugs, Elsevier, Amsterdam.Google Scholar
- 10.Chang, C. S. and Tsai, S. W. (1997), Appl. Biochem. Biotechnol., Part A: Enzyme Eng. Biotechnol. 68, 135–142.Google Scholar
- 11.Tsai, S. W. and Wei, H. J. (1993), J. Liq. Chromatogr. 16, 2993–3001.Google Scholar
- 16.Tsai, S. W. and Wei, H. J. (1994), Biocatalysis 11, 33–45.Google Scholar
- 17.Dordick, J. S. (1990), in Applied Biocatalysis, vol. 1, Blanch, H. W. and Clark, D. S., eds., Marcel Dekker, New York, pp. 1–52.Google Scholar