Skip to main content

Asymmetrically Substituted myo-Inositols. XXXIX. The Synthesis of Conjugate of 2',3'-Didehydro-3'-deoxythymidine with Phosphatidylinositol: A New Nucleoside Phospholipid with Potential Anti-HIV Activity

Abstract

A partially protected phosphatidylinositol with a free hydroxyl group in the cyclitol moiety was synthesized by phosphorylation of a tetrasubstituted myo-inositol using the H-phosphonate and phosphoamidite methods. The H-phosphonate method was advantageous for the synthesis of selectively protected monophosphoinositide due to a lesser number of stages. Two schemes for the conjugation of 2',3'-didehydro-3'-de oxythymidine with phosphatidylinositol using succinic acid as a linker were tested in the synthesis of the target nucleoside phospholipid.

This is a preview of subscription content, access via your institution.

References

  1. Shastina, N.S., Einisman, L.I., Stepanov, A.E., and Shvets, V.I., Bioorg. Khim., 1996, vol. 22, pp. 446–450.

    Google Scholar 

  2. De Clercq, E., Clin. Microbiol. Rev., 1997, vol. 10, pp. 674–693.

    Google Scholar 

  3. Siddiqui, A.Q., McGuigan, Ch., Ballatore, C., Zuccotto, F., Gilbert, I.H., De Clercq, E., and Balzarini, J., J. Med. Chem., 1999, vol. 42, pp. 4122–4128.

    Google Scholar 

  4. Dessolin, J., Galea, P., Vlieghe, P., Chermann, J.-C., and Kraus, J.-L., J. Med. Chem., 1999, vol. 42, pp. 229–241.

    Google Scholar 

  5. Vodovozova, E.L., Pavlova, Yu.B., Polushkina, M.A., Rzhaninova, A.A., Garaev, M.M., and Molotkovsky, Yul.G., Bioorg. Khim., 1996, vol. 22, pp. 451–457.

    Google Scholar 

  6. Ryakhovskii, V.V., Malekin, S.I., Nosova, V.M., Kisin, A.V., Kruglyak, Yu.L., and Kurochkin, V.K., Bioorg. Khim., 1999, vol. 25, pp. 499–504.

    Google Scholar 

  7. Schott, H., Ludwig, P.S., Immelmann, A., and Schwendener, R.A., Eur. J. Med. Chem., 1999, vol. 34, pp. 343–352.

    Google Scholar 

  8. Jan, S.T., Shin, M.J., Venkatachalam, T.K., Dcruz, O.J., Chen, C.L., and Uckun, F.M., Antivir. Chem. Chemother., 1999, vol. 10, pp. 39–46.

    Google Scholar 

  9. Kucera, G.L., Goff, C.L., Iyer, N., Morrisnatschke, S., Ishaq, K.S., Wyrick, S.D., Fleming, R.A., and Kucera, L.S., Antivir. Res., 2001, vol. 50, pp. 129–137.

    Google Scholar 

  10. Mavromoustakos, T., Calogeropoulou, T., Koufaki, M., Kolocouris, A., Daliani, I., Demetzos, C., Meng, Z.X., Makriyannis, A., Balzarini, J., and De Clercq, E., J. Med. Chem., 2001, vol. 44, pp. 1702–1709.

    Google Scholar 

  11. Mitsuya, H. and Broder, S., Nature, 1987, vol. 325, p. 773.

    Google Scholar 

  12. Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H., and Richman, D.D., J. Biol. Chem., 1990, vol. 265, pp. 6112–6117.

    Google Scholar 

  13. McGuigan, C., Pathirana, R.N., Mahmood, N., Devine, K.G., and Hay, A.J., Antivir. Res., 1992, vol. 17, pp. 311–321.

    Google Scholar 

  14. Siddiqui, A.Q., McGuigan, C., Ballatore, C., De Clercq, E., and Balzarini, J., J. Med. Chem., 1999, vol. 42, pp. 393–399.

    Google Scholar 

  15. Berezovskaya, Yu., Chudinov, M., Kirillova, Yu., Shastina, N., Shvets, V., and Yurkevich, A., Nucleosides Nucleotides, 1998, vol. 17, pp. 3777–3783.

    Google Scholar 

  16. Berrige, M.J., Annu. Rev. Biochem., 1987, vol. 56, pp.-59–193.

    Google Scholar 

  17. Shvets, V.I., Stepanov, A.E., Krylova, V.N., and Gulak, P.V., mio-Inozit i fosfoinozitidy (myo-Inositol and Phosphoinositides), Moscow: Nauka, 1987.

    Google Scholar 

  18. Stepanov, A.E. and Shvets, V.I., Bioorg. Khim., 1998, vol. 24, pp. 731–746.

    Google Scholar 

  19. Ceolotto, C., Flekt, W., and Schorsch, F.J., Biochim. Biophys. Acta, Bio-Membr., 1996, vol. 1285, pp. 71–78.

    Google Scholar 

  20. Tremblay, J.M., Helmkamp, G.M., and Yarbrough, L.R., J. Biol. Chem., 1996, vol. 271, pp. 21 075–21 080.

    Google Scholar 

  21. Klyashchitskii, B.A., Shvets, V.I., and Preobrazhenskii, N.A., Chem. Phys. Lipids, 1969, vol. 3, pp. 394–400.

    Google Scholar 

  22. IUPAC-IUB Comission on Biochemical Nomenclature (CBN), Eur. J. Biochem., 1967, vol. 2, p. 127.

    Google Scholar 

  23. Zamyatina, A.Yu., Bushnev, A.S., and Shvets, V.I., Bioorg. Khim., 1994, vol. 20, pp. 1253–1295.

    Google Scholar 

  24. Shastina, N.S., Einisman, L.I., Kashiricheva, I.I., Stepanov, A.E., and Shvets, V.I., Bioorg. Khim., 1995, vol. 21, pp. 641–650.

    Google Scholar 

  25. Falck, J.R., Krishna, U.M., Katipally, K.R., Capdevila, J.H., and Ulug, E.T., Tetrahedron Lett., 2000, vol. 41, pp. 4271–4275.

    Google Scholar 

  26. De Almedia, M.V., Cleophax, J., Gateau-Olesker, A., Prestat, G., Dubreuil, D., and Gero, S.D., Tetrahedron, 1999, vol. 55, pp. 12 997–13 010.

    Google Scholar 

  27. Lindh, I. and Stawinski, J., J. Org. Chem., 1989, vol. 54, pp. 1338–1342.

    Google Scholar 

  28. Shvets, V.I., Klyashchitskii, B.A., Stepanov, A.E., and Evstigneeva, R.P., Tetrahedron, 1973, vol. 29, p. 331.

    Google Scholar 

  29. Bruzik, K.S., Salamonczyk, G., and Stec, W.J., J. Org. Chem., 1986, vol. 52, pp. 2368–2370.

    Google Scholar 

  30. Gigg, J., Gigg, R., and Conant, R., Carbohydr. Res., 1985, vol. 142, pp. 132–134

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. S. Shastina.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shastina, N.S., Tuchnaya, O.A., Einisman, L.I. et al. Asymmetrically Substituted myo-Inositols. XXXIX. The Synthesis of Conjugate of 2',3'-Didehydro-3'-deoxythymidine with Phosphatidylinositol: A New Nucleoside Phospholipid with Potential Anti-HIV Activity. Russian Journal of Bioorganic Chemistry 29, 267–273 (2003). https://doi.org/10.1023/A:1023988500659

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1023988500659

  • myo-inositol
  • phosphatidylinositol
  • H-phosphonate method
  • 2',3'-didehydro-3'-deoxythymidine
  • phosphoamidite method