Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and Antiviral Activity of Novel C-Methyl Branched Cyclopropyl Nucleosides

  • Published : 2003.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

A series of novel cyclopropyl nucleosides was synthesized using the highly stereoselective Simmons-Smith reaction starting from 1,2:5,6-di-Ο-isopropylidene-D-mannitol. The structural assignments of these nucleosides were determined by NMR studies and X-ray crystallography. All the synthesized nucleosides were assayed against several viruses.

Keywords

References

  1. Arimilli, M. N., Kim, C. U., Dougherty, J., Mulato, A., Oliyai, R., Shaw, J. P., Cundy, K. C., and Bischofberger, N., Synthesis, in vitro biological evaluation and oral bioavailability of 9-[2-[(phosphonomethoxy)propyl]adenine (PMPA) prodrugs. Antivir. Chem. Chemother., 8, 557-564 (1997) https://doi.org/10.1177/095632029700800610
  2. Chu, C. K., Ma, T. W., Shanmuganathan, K., Wang, C.-G., Xiang, Y.-J., Pai, S. B., Yao, G.-Q., Sommadossi, J.-P., and Cheng, Y.-C., Use of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil as a novel antiviral agent for hepatitis B virus and Epstein-Barr virus. Antimicrob. Agents Chemother., 39, 979-981(1995) https://doi.org/10.1128/AAC.39.4.979
  3. 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., 1592U89, A novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity. Antimicrob. Agents Chemother., 41, 1082-1093 (1997)
  4. Dienstag, J. L., Perrillo, R. P., Schiff, E. R., Bartholomew, M., Vicary, C., and Rubin, M. A., Preliminary trial of lamivudine for chronic hepatitis B infection. New Engl. J. Med., 333, 1657-1661 (1995) https://doi.org/10.1056/NEJM199512213332501
  5. Furman, P. A., Fyfe, J. A., St. Clair, M. H., Weinhold, K., Rideout, J. L., Freeman, G. A., Lehrman, S. N., Bolognesi, D. P., Broder, S., Mitsuya, H., and Barry, D. W., Phosphorylation of 3'-azido-3'-deoxythymine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. Proc. Natl. Acad. Sci. U.S.A., 83, 8333-8337 (1986) https://doi.org/10.1073/pnas.83.21.8333
  6. Hong, J. H., Gao, M. Y., Choi, Y., Cheng, Y. C., Schinazi, R. F., and Chu, C. K., Synthesis of novel 3'-C-methyl-apionucleosides: an asymmetric construction of a quaternary carbon by Claisen rearrangement. Carbohydr. Res., 328, 37-48 (2000) https://doi.org/10.1016/S0008-6215(00)00005-7
  7. Hossain, N., Rozenski, J., De Clercq, E., and Herdewjn, P., Synthesis and antiviral activity of acyclic analogues of 1,5-anhydrohexitol nucleosides using Mitsunobu reaction. Tetrahedron, 52, 13655-13670 (1996) https://doi.org/10.1016/0040-4020(96)00818-6
  8. Hukuyama, Y., Hirono, M., and Kodama, M., Total synthesis of (+)-bicyclohumulenone. Chemistry Letter, 167-170 (1992)
  9. Iwayama, S., Ono, N., Ohmura, Y., Suzuki, K., Aoki, M., Nakazawa, H., Oikawa, M., Kata, T., Okunishi, M., Nishiyama, Y., and Yamanishi, K., Antiherpesvirus activities of (1'S, 2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl] guanine. Antimicrob. Agents Chemother., 42, 1666-1670 (1998)
  10. Jeon, G. S. and Nair, V., New isomeric analogues of anti-HIV active azidonucleosides. Tetrahedron, 52, 12643-12650 (1996) https://doi.org/10.1016/0040-4020(96)00766-1
  11. Kjellberg, J. and Johansson, N. G., Characterization of $N^7$ and $N^9$ alkylated analogues by $^1H-$ and $^{13}C$-NMR. Tetrahedron, 42, 6541-6544 (1986) https://doi.org/10.1016/S0040-4020(01)88116-3
  12. Lin, T.-S., Schinazi, R. F., and Prusoff, W. H., Potent and selective in vitro activity of 3'-deoxythymidin-2-ene (3'-deoxy-2',3'-didehydrothymidine) against human immunodeficiency virus. Biochem. Pharmacol., 36, 2713-2718 (1987) https://doi.org/10.1016/0006-2952(87)90253-X
  13. Lin, T. S., Luo, M. Z., Liu, M. C., Pai, S. B., Dutschman, G. E., and Cheng, Y.-C., Synthesis and biological evaluation of 2',3'-dideoxy-L-pyrimidine nucleosides as potential antiviral agents against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). J. Med. Chem., 37, 798-803 (1994) https://doi.org/10.1021/jm00032a013
  14. Morikawa, T., Sasaki, H., Mori, K., Shiro, M., and Taguchi, T., Simmons-Smith reaction of fluoroallyl alcohol derivatives. Chem. Pharm. Bull., 40, 3189-3193 (1992) https://doi.org/10.1248/cpb.40.3189
  15. Qiu, Y. L., Ksebati, M. B., Ptak, R. G., Fan, B. Y., Breitenbach, J. M., Lin, J. S., Cheng, Y. C., Kern, E. R., Drach, J. C., and Zemlicka, J., (Z)- and (E)-2-[(Hydroxymethyl)cyclopropylidene] methyladenine and guanine. New nucleoside analogues with a broad-spectrum antiviral activity. J. Med. Chem., 41, 10-23 (1998) https://doi.org/10.1021/jm9705723
  16. 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-1 in human lymphocytes. Antimicrob. Agents Chemother., 36, 672-676 (1992) https://doi.org/10.1128/AAC.36.3.672
  17. Sekiyama, T., Hatsuya, S., Tanaka, Y., Uchiyama, M., Ono, N., Iwayama, S., Oikawa, M., Suzuki, K., Okunishi, M., and Tsuji, T., Synthesis and antiviral activity of novel acyclic nucleosides: discovery of cyclopropyl nucleoside with potent inhibitory activity against herpesviruses. J. Med. Chem., 41, 1284-1298 (1998) https://doi.org/10.1021/jm9705869
  18. Yarchoan, R., Perno, C. F., Thomas, R. V., Klecker, R. W., Allain, J.-P., Wills, R. J., McAtee, N., Fischl, M. A., Dubinsky, R., McNeely, M. C., Mitsuya, H., Lawley, T. J., Safai, B., Myers, C. E., Pluda, J. M., Leuther, M., Collins, J. M., and Broder, S., Phase 1 studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). Lancet, 1, 76-81 (1998)
  19. 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) https://doi.org/10.1126/science.2502840