Novel phenyl branched apiosyl nucleosides were synthesized in this study. The introduction of phenyl group in the 4'-position was accomplished by a [3,3]-sigmatropic rearrangement. Apiosyl sugar moiety was constructed by sequential ozonolysis and reductions. The natural bases (cytosine and adenine) were efficiently coupled with an apiosyl sugar by classical glycosyl condensation procedure (persilyated base and TMSOTf). The antiviral activities of the synthesized compounds were evaluated against the HIV-1, HSV-1, HSV-2 and HCMV.
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Daluge, S. M., Good, S. S., Faletto, M. B., Miller, W. H., St Clair, M. H., Boone, L. R., Tisdale, M., Parry, N. R., Reardon, J. E., Dornsife, R. E., Averett, D. R., and Krenitsky, T. A., A novel carbocyclic nucleoside analog with potent, selective antihuman immunodeficiency virus activity.Antimicrob. Agents Chemother., 41, 1082–1093 (1997).
Fuman, P. A., Fyfe, J. A., St. Clair, M. H., Weinhold, K., Rideout, J. L., Freeman, G. A., Nusinoff-Lehrman, S., Bolognesi, D. P., Broder, S., Mitsuya, H., and Barry, D. W., Phosphorylation of 3¢-azido-3¢-deoxythymidine and selective interaction of the 5¢-triphosphate with human immunodeficiency virus reverse transcriptase.Proc. Natl. Acad. Sci. U.S.A., 83, 8333–8337 (1986).
Hong, J. H. and Ok, O. H., Synthesis of 4'-α-C phenyl-branched carbocyclic nucleoside using ring-closing metathesis.Bull. Korean Chem. Soc., 24, 1289–1292 (2003).
Lin, T.-S., Schinazi, R. F., and Prusoff, W. H., Potent and selectivein vitro activity of 3′-deoxy thymidine-2′-ene (3′-deoxy-2′, 3′-dideoxydehydrothymidine) against human immunodeficiency virus.Biochem. Pharmacol., 36, 2713–2718 (1987).
Nair, V. and Tahnke, T., Antiviral activities of isomeric dideoxynucleosides ofd- andl-related stereochemistry.Antimicrob. Agents Chemother., 39, 1017–1029 (1995).
Nair, V., Zintek, L. B., Sells, T. B., Jeffery, A. L., Nuesca, Z. M., Purdy, D. F., Jeon, G. S., Hamilton, R. B., Bolon, P. J., and Malany, S., Novel chiral isomeric nucleosides and nucleotides: Synthesis, enzymology, and anti-HIV activity.Antiviral Res., 23, 38–38 (1994).
Ohrui, H., Kohgo, S., Kitano, K., Sakata, S., Kodama, E., Yoshimura, K., Matsuoka, M., Shigeta, S., and Mitsuya, H., Synthesis of 4′-C-ethynyl-β-d-arabino- and 4′-C-ethynyl-2′-deoxy-β-d-ribo-pentofuranosylpyrimidines and- purines and evaluation of their anti-HIV activity.J. Med. Chem., 43, 4516–4525 (2000).
O-Yang, C., Wu, H. Y., Fraser-Smith, E. B., and Walker, K. A. M., Synthesis of 4′-cyanothymidine and analogs as potent inhibitors of HIV.Tetrahedron Lett., 33, 37–40 (1992).
Schinazi, R. F., Chu, C. K., Peck, A., McMillan, A., Mathis, R., Cannon, D., Jeong, L. S., Beach, J. W., Choi, W. B., Yeola, S., and Liotta, D. C., Activities of the four optical isomers of 2′, 3′-dideoxy-3′-thiacytidine (BCH-189) against human immunodeficiency virus type I in human lymphocytes.Antimicrob. Agents Chemother., 36, 672–676 (1992).
Sells, T. B. and Nair, V., Synthetic approaches to novel isomeric dideoxynucleosides containing a chiral furanethanol carbohydrate moiety.Tetrahedron Lett., 34, 3527–3530 (1993).
Sugimoto, I., Shuto, S., Mori, S., Shigeta, S., Matuda, A., Synthesis of 4′α-branched thymidines as a new type of antiviral agents.Bioorg. Med. Chem. Lett., 9, 385–388 (1999).
Yarchoan, R., Mitsuya, H., Thomas, R. V., Pluda, J. M., Hartman, N. R., Perno, C. F., Marczyk, K. S., Allain, J.-P., Johns, D. G., and Broder, S.,In vivo activity against HIV and favorable toxicity profile of 2′,3′-dideoxyinosine.Science, 245, 412–415 (1989).
Yarchoan, R., Thomas, R. V., Allain, J.-P., McAtee, N., Dubinsky, R., Mitsuya, H., Lawley, T. J., Safai, B., Myers, C. E., Perno, C. F., Klecker, R. W., Wills, R. J., Fischl, M. A., McNeely, M. C., Pluda, J. M., Leuther, M., Collins, J. M., and Broder, S. The phase 1 studies of 2′,3′-dideoxycytidine in human immunodeficiency virus infection as single agent and alternating with zidovudine (AZT).Lancet, 1, 76–81 (1988).
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Kim, J.W., Hong, J.H. Synthesis and antiviral activity of novel phenyl branched apiosyl nucleosides. Arch Pharm Res 29, 464–468 (2006). https://doi.org/10.1007/BF02969417
- Apiosyl nucleoside
- Antiviral agents