Archives of Pharmacal Research

, Volume 26, Issue 12, pp 990–996 | Cite as

Synthesis of novel carboacyclic nucleosides with vinyl bromide moiety as open-chain analogues of neplanocin A



A novel carboacyclic nucleoside analogue, 9-[2-bromo-4-hydroxy-3-hydroxymethyl-2-butenyl] adenine, and its derivatives were designed and synthesized as open-chain analogues of neplanocin A. The syntheses were accomplished via the coupling of adenine or pyrimidine bases to the key intermediate allylic bromide 7. The bromide 7 was prepared from epichlorohydrin in a seven step process in a 54% overall yield. The synthesized compounds were evaluated for their antiviral activity against the polio virus, HSV and HIV.

Key words

Carboacyclic nucleoside Neplanocin A Antiviral Open-chain analog 


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  1. Borcherding, D. R., Narayanan, S., Hasobe, M., McKee, J. G., Keller, B. T., and Borchardt, R. T., Potential inhibitors of S adenosylmethionine-dependent methyltransferases. II. Molecular dissections of neplanocin A as potential inhibitors of S-adenosylhomocysteine hydrolase.J. Med. Chem., 31, 1729–1738 (1988).PubMedCrossRefGoogle Scholar
  2. Borcherding, D. R., Scholtz, S. A., and Borchardt, R. T., Synthesis of analogues of neplanocin A: Utilization of optically active dihydroxycyclopentenones derived from carbohydrates.J. Org. Chem., 52, 5457–5461 (1987).CrossRefGoogle Scholar
  3. Branson, J. J., Ghazzouli, I., Hitchcock, M. J. M., Webb, R. R., and Martin, J. C., Synthesis and antiviral activity of the nucleotide analogue (S)-1 -[3-hydroxy-2-(phosphonylmethoxy) propyl]cytosine.J. Med. Chem., 32, 1457–1463 (1989).CrossRefGoogle Scholar
  4. Cook, A. F. and Holman, M. J., Fluorinated pyrimidine nucleosides. 4. Synthesis and antitumor testing of a series of 2′,5′-dideoxy- and 2′,3′,5′-trideoxynucleosides of 5-fluorouracil.J. Med. Chem., 23, 852–857 (1980).PubMedCrossRefGoogle Scholar
  5. Corey, E. J. and Kim, C. U., A new and highly effective method for the oxidation of primary and secondary alcohols to carbonyl compounds.J. Am. Chem. Soc., 94, 7586–7587 (1972).CrossRefGoogle Scholar
  6. Harnden, M. R., Jarvest, R. L., Bacon, T. H., and Boyd M. R., Synthesis and antiviral activity of 9-[4-hydroxy-3-(hydroxymethyl) but-1-yl]purines.J. Med. Chem., 30, 1636–1642 (1987).PubMedCrossRefGoogle Scholar
  7. Hronowski, L. J. J. and Szarek, W. A., Synthesis of cyclopentane analogs of 5-fluorouracil nucleosides.Can. J. Chem., 70, 1162–1169 (1992).CrossRefGoogle Scholar
  8. Marquez, V. E.,Carbocyclic nucleosides. In advances in antiviral drug design, JAI Press, 1996, Vol. 2, pp 89–146, and references therein.CrossRefGoogle Scholar
  9. Marquez, V. E., Lim, M.-l., Treanor, S. P., Plowman, J., Priest, M. A., Markovac, A., Khan M. S., Kaskar, B., and Driscoll, J. S., Cyclopentenylcytosine. A carbocyclic nucleoside with antitumor and antiviral properties.J. Med. Chem., 31, 1687–1694 (1988).PubMedCrossRefGoogle Scholar
  10. Ogilvie, K. K., Hamilton, R. G., Gillen M. F., and Radatus B. K., Uracil analogues of the acyclonucleoside 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine(BIOLF-62).Can. J. Chem., 62, 16–21 (1984).CrossRefGoogle Scholar
  11. Phadtare, S., Kessel, D., Corbett, T. H., Renis, H. E., Court, B. A., and Zemlicka, J., Unsaturated and carbocyclic nucleoside analogues: synthesis, antitumor, and antiviral activity.J. Med. Chem., 34, 421–429 (1991).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2003

Authors and Affiliations

  1. 1.College of PharmacySookmyung Women’s UniversitySeoulKorea

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