Skip to main content
SpringerLink
Log in

Highly Regioselective Synthesis of 3′-O-Acyl-Trifluridines Catalyzed by Pseudomonas cepacia Lipase

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

3′-O-Acyl-trifluridines were prepared successfully through an enzymatic approach for the first time. Among the ten commercially available lipases tested, Pseudomonas cepacia lipase displayed the highest regioselectivity towards the acylation of 3′-hydroxyl of trifluridine. Furthermore, the effects of some crucial factors on the enzymatic myristoylation of trifluridine were examined. The optimal reaction medium, molar ratio of trifluridine to vinyl myristate and reaction temperature were found to be anhydrous THF, 1:7 and 50 °C, under which the reaction rate, substrate conversion, and 3′-regioselectivity were 63.9 mM/h, >99.0%, and 99%, respectively. Additionally, the enzyme recognition of the chain length of the acyl donors was investigated. The results showed that 3′-regioselectivity of the enzyme maintained 99% with the increment of acyl chain length (C6, C10, and C14). The reason might derive from the strong hydrophobic interaction between 5-CF3 group of the base moiety and Leu 287 located in the medium-sized pocket of the active site.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Anand, B. S., Katragadda, S., Gunda, S., & Mitra, A. K. (2006). Molecular Pharmaceutics, 3, 431–440.

    Article  CAS  Google Scholar 

  2. Altmann, S., Brandt, C. R., Murphy, C. J., Patnaikuni, R., Takla, T., Toomey, M., et al. (2011). Journal of Infectious Diseases, 203, 683–690.

    Article  CAS  Google Scholar 

  3. De Clercq, E. (2011). Annual Review of Pharmacology and Toxicology, 51, 1–24.

    Article  Google Scholar 

  4. Carmine, A. A., Brogden, R. N., Heel, R. C., Speight, T. M., & Avery, G. S. (1982). Drugs, 23, 329–353.

    Article  CAS  Google Scholar 

  5. Hobden, J. A., Kumar, M., Kaufman, H. E., Clement, C., Varnell, E. D., Bhattacharjee, P. S., et al. (2011). Investigative Ophthalmology & Visual Science, 52, 830–833.

    Article  CAS  Google Scholar 

  6. Skevaki, C. L., Galani, I. E., Pararas, M. V., Giannopoulou, K. P., & Tsakris, A. (2011). Drugs, 71, 331–347.

    Article  Google Scholar 

  7. Sangwan, V. S., & Basu, S. (2011). British Journal of Ophthalmology, 95, 1–2.

    Article  Google Scholar 

  8. Mencucci, R., Paladini, I., Menchini, U., Gicquel, J. J., & Dei, R. (2011). British Journal of Ophthalmology, 95, 28–31.

    Article  CAS  Google Scholar 

  9. Kumar, V., Parmar, V. S., & Malhotra, S. V. (2010). Biochimie, 92, 1260–1265.

    Article  CAS  Google Scholar 

  10. Gotor, V. (2002). Organic Process Research and Development, 6, 420–426.

    Article  CAS  Google Scholar 

  11. Li, N., Smith, T. J., & Zong, M. H. (2010). Biotechnology Advances, 28, 348–366.

    Article  CAS  Google Scholar 

  12. Hamamura, E. K., Prystasz, M., Verheyden, J. P. H., Moffatt, J. G., Yamaguchi, K., Uchida, N., et al. (1976). Journal of Medicinal Chemistry, 19, 654–662.

    Article  CAS  Google Scholar 

  13. Ferrero, M., & Gotor, V. (2000). Monatshefte Für Chemie, 131, 585–616.

    CAS  Google Scholar 

  14. Díaz-Rodríguez, A., Fernández, S., Sanghvi, Y. S., Ferrero, M., & Gotor, V. (2006). Organic Process Research and Development, 10, 581–587.

    Article  Google Scholar 

  15. Quan, J., Wang, N., Cai, X. Q., Wu, Q., & Lin, X. F. (2007). Journal of Molecular Catalysis B: Enzymatic, 44, 1–7.

    Article  CAS  Google Scholar 

  16. Ozaki, S., Akiyama, T., Morita, T., Kumegawa, M., Nagase, T., Uehara, N., et al. (1990). Chemical & Pharmaceutical Bulletin, 38, 3164–3166.

    CAS  Google Scholar 

  17. Ferrero, M., & Gotor, V. (2000). Chemical Reviews, 100, 4319–4348.

    Article  CAS  Google Scholar 

  18. Lavandera, I., Fernandez, S., Magdalena, J., Ferrero, M., Kazlauskas, R. J., & Gotor, V. (2005). ChemBioChem, 6, 1381–1390.

    Article  CAS  Google Scholar 

  19. Lavandera, I., Fernandez, S., Magdalena, J., Ferrero, M., Grewal, H., Savile, C. K., et al. (2006). ChemBioChem, 7, 693–698.

    Article  CAS  Google Scholar 

  20. Kim, K. K., Song, H. K., Shin, D. H., Hwang, K. Y., & Suh, S. W. (1997). Structure, 5, 173–185.

    Article  CAS  Google Scholar 

  21. Klibanov, A. M. (1997). Trends in Biotechnology, 15, 97–101.

    Article  CAS  Google Scholar 

  22. Klibanov, A. M. (2001). Nature, 409, 241–246.

    Article  CAS  Google Scholar 

  23. Wang, Z. Y., Li, N., & Zong, M. H. (2009). Journal of Molecular Catalysis B: Enzymatic, 59, 212–219.

    Article  CAS  Google Scholar 

  24. Weber, H. K., Weber, H., & Kazlauskas, R. J. (1999). Tetrahedron-Asymmetry, 10, 2635–2638.

    Article  CAS  Google Scholar 

  25. Wang, Z. Y., & Zong, M. H. (2009). Biotechnology Progress, 25, 784–791.

    Article  Google Scholar 

  26. Li, N., Zong, M. H., & Ma, D. (2009). Tetrahedron, 65, 1063–1068.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the Natural Science Research Project of Higher Education of Jiangsu (grant no. 10KJB530001), National Natural Science Foundation of China (grant nos. 20676043 and 20876059), and Science and Technology Project of Guangzhou city (grant no. 2007Z3-E4101) for financial support.

Author information

Authors and Affiliations

  1. School of Life Science and Chemical Engineering, Huaiyin Institute of Technology, Huai’an, 223003, People’s Republic China

    Zhao-Yu Wang & Yan-Hong Bi

  2. Lab of Applied Biocatalysis, South China University of Technology, Guangzhou, 510640, People’s Republic China

    Zhao-Yu Wang & Min-Hua Zong

Authors
  1. Zhao-Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan-Hong Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min-Hua Zong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhao-Yu Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, ZY., Bi, YH. & Zong, MH. Highly Regioselective Synthesis of 3′-O-Acyl-Trifluridines Catalyzed by Pseudomonas cepacia Lipase. Appl Biochem Biotechnol 165, 1161–1168 (2011). https://doi.org/10.1007/s12010-011-9333-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-011-9333-9

Keywords

Search

Navigation