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

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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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References

  1. Federsel, H. J. (1993), CHEMTECH 12, 24–33.

    Google Scholar 

  2. Margolin, A. J. (1993), Enzyme Microb. Technol. 15, 266–280.

    Article  CAS  Google Scholar 

  3. Hutt, A. J. and Caldwell, J. (1984), Clin. Pharmacokinet. 9, 371–373.

    CAS  Google Scholar 

  4. Shanbhag, V. R., Crider, A. M., Gokhale, R., Harpalani, A., and Dick, R. M. (1992), J. Pharm. Sci. 81, 149–154.

    Article  CAS  Google Scholar 

  5. Bundgaard, H. (1985), Design of Prodrugs, Elsevier, Amsterdam.

    Google Scholar 

  6. Nielsen, N. N. and Bundgaard, H. (1988), J. Pharm. Sci. 77, 285–298.

    Article  CAS  Google Scholar 

  7. Tammara, V. K., Narurkar, M. M., Crider, A. M., and Khan, A. M. (1993), Pharm. Res. 10, 1191–1199.

    Article  CAS  Google Scholar 

  8. Chang, C. S. and Tsai, S. W. (1997), Enzyme Microb. Technol. 20, 635–639.

    Article  CAS  Google Scholar 

  9. Tsai, S. W., Lin, J. J., Chang C. S., and Chen, J. P. (1997), Biotechnol. Prog. 13, 82–88.

    Article  CAS  Google Scholar 

  10. Chang, C. S. and Tsai, S. W. (1997), Appl. Biochem. Biotechnol., Part A: Enzyme Eng. Biotechnol. 68, 135–142.

    CAS  Google Scholar 

  11. Tsai, S. W. and Wei, H. J. (1993), J. Liq. Chromatogr. 16, 2993–3001.

    CAS  Google Scholar 

  12. Allenmark, S. and Ohlsson, A. (1992), Chirality 4, 98–102.

    Article  CAS  Google Scholar 

  13. Nielsen, N. M. and Bundgaard, H. (1987), Int. J. Pharm. 39, 75–85.

    Article  CAS  Google Scholar 

  14. Rizzi, M. P., Stylos, P., and Reuss, M. (1992), Enzyme Microb. Technol. 14, 709–714.

    Article  CAS  Google Scholar 

  15. Chen, C. S., Fujimoto, Y., Girdaukas, G., and Sih, C. J. (1982), J. Am. Chem. Soc. 104, 7294–7299.

    Article  CAS  Google Scholar 

  16. Tsai, S. W. and Wei, H. J. (1994), Biocatalysis 11, 33–45.

    CAS  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 

  18. Halling, P. (1994), Enzyme Microb. Technol. 16, 178–206.

    Article  CAS  Google Scholar 

  19. Phillips, R. S. (1992), Enzyme Microb. Technol. 14, 417–419.

    Article  CAS  Google Scholar 

  20. Palomer, A., Cabre, M., Ginesta, J., Mauleon, D., and Carganico, G. (1993), Chirality 5, 320–328.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical Engineering, National Cheng Kung University, 70101, Tainan Taiwan, Republic of China

    Shau-Wei Tsai, Chin-Shain Tsai & Chun-Sheng Chang

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  1. Shau-Wei Tsai
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  2. Chin-Shain Tsai
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  3. Chun-Sheng Chang
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Correspondence to Shau-Wei Tsai.

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Tsai, SW., Tsai, CS. & Chang, CS. Lipase-catalyzed synthesis of (S)-naproxen ester prodrug by transesterification in organic solvents. Appl Biochem Biotechnol 80, 205–219 (1999). https://doi.org/10.1385/ABAB:80:3:205

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  • DOI: https://doi.org/10.1385/ABAB:80:3:205

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