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.
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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).
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).
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).
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).
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).
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).
Hronowski, L. J. J. and Szarek, W. A., Synthesis of cyclopentane analogs of 5-fluorouracil nucleosides.Can. J. Chem., 70, 1162–1169 (1992).
Marquez, V. E.,Carbocyclic nucleosides. In advances in antiviral drug design, JAI Press, 1996, Vol. 2, pp 89–146, and references therein.
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).
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).
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).
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Choi, M., Kim, H. Synthesis of novel carboacyclic nucleosides with vinyl bromide moiety as open-chain analogues of neplanocin A. Arch Pharm Res 26, 990–996 (2003). https://doi.org/10.1007/BF02994747
- Carboacyclic nucleoside
- Neplanocin A
- Open-chain analog