Abstract
Novel 9-[2-fluoro-4-hydroxy-3-hydroxymethyl-2-butenyl]adenine and its related compounds were designed and synthesized as open-chain analogues of neplanocin A. Alkylation of adenine or pyrimidine bases with the mesylate4 was chosen as a simple approach to the synthesis of 2-fluoro-2-butenylated nucleosides. Mesylate4 was prepared from dihydroxyacetone dimervia four steps in 58% overall yield. The synthesized compounds were evaluated their antiviral activity against HSV, HIV and Polio viruses.
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References Cited
Blackburn, G. M., Kent, D. E., Synthesis of α- and γ-fluoroalkylphosphonates.J. Chem. Soc. (Perkin I), 913–917 (1986).
Borcherding, D. R., Narayanan, S., Hasobe, M., McKee, J. G., Keller, B. T., 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., Borchardt, R. T., Synthesis of analogues of neplanocin A: Utilization of optically active dihydroxycyclopentenones derived from carbohydrates.J. Org. Chem., 52, 5457–5461 (1987).
Bronson, J. J., Ghazzouli, I., Hitchcock, M. J. M., Webb, R. R., 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).
Casara, P. J., Kenny, M. T., Jund, K. C., Synthesis of acid stable fluorinated acyclonucleosides as potential antiviral agents.Tetrahedron Lett., 32, 3823–3826 (1991), and references cited therein.
Cook, A. F., 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).
De Clercq, E., Cools, M., Balzarini, J., Marquez, V. E., Bocherding, D. R., Bochardt, R. T., Drach, J. C., Kitaoka, S., Konno, T., Broad-spectrum antiviral activities of neplanocin A, 3-deazaneplanocin A, and their 5′-nor derivatives.Antimicrob. Agents Chemother., 33, 1291–1297 (1989).
Harnden, M. R., Jarvest, R. L., Bacon, T. H., 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., Szarek, W. A., Synthesis of cyclopentane analogs of 5-fluorouracil nucleosides.Can. J. Chem., 70, 1162–1169 (1992).
Hua, M., Korkowski, P. M., Vince, R., Synthesis and biological evaluation of acyclic neplanocin analogues.J. Med. Chem., 30, 198–200 (1987).
Marquez, V. E., Carbocyclic nucleosides. In advances in antiviral drug design, JAI Press, 1996, Vol. 2, pp 89–146, and references therein.
Ogilvie, K. K., Hamilton, R. G., Gillen M. F., Radatus, B. K., Uracil analogues of the acyclonucleoside 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine (BIOLF-62).Can. J. Chem., 62, 16–21 (1984).
Phadtare, S., Kessel, D., Corbett, T. H., Renis, H. E., Court, B. A., Zemlicka, J., Unsaturated and carbocyclic nucleoside analogues: Synthesis, antitumor, and antiviral activity.J. Med. Chem., 34, 421–429 (1991).
Thenappan, A., Burton, D. J., Acylation of fluorocarbethoxy substituted ylids: A simple and general route to α-fluoro β-keto esters.J. Org. Chem., 56, 273–277 (1991).
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Choi, MH., Kim, HD. Synthesis and biological evaluation of 9-[2-fluoro-4-hydroxy-3-hydroxymethyl-2-butenyl]adenine and its related compounds as open-chain analogues of neplanocin A. Arch. Pharm. Res. 20, 501–506 (1997). https://doi.org/10.1007/BF02973948
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DOI: https://doi.org/10.1007/BF02973948