Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and Antiviral Activity of Novel Anomeric Branched Carbocyclic Nucleosides

  • Published : 2005.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

Novel anomeric branched carbocyclic nucleosides were synthesized from 1,3-dihydroxy acetone. 4'-Hydroxymethyl was installed by [3,3]-sigmatropic rearrangement reaction and 1'-methyl group was introduced by carbonyl addition of methylmagnesium bromide. The coupling of nucleosidic bases and desilylation afforded a series of novel nucleosides. The synthesized compounds $16{\~}19$ were evaluated for their antiviral activity against HIV-1, HSV-1, HSV-2, and EMCV. Compounds 16 and 19 exhibit toxicity non-related to any anti-HIV-1 activity.

Keywords

References

  1. Agrofoglio, L., Suhas, E., Farese, A., Condom, R., Challand, S., and Earl, R. A., Synthesis of carbocyclic nucleosides. Tetrahedron, 50, 10611-10670 (1994) https://doi.org/10.1016/S0040-4020(01)89258-9
  2. Borthwick, A. D. and Biggadike, K., Synthesis of chiral carbocyclic nucleoside. Tetrahedron, 48, 571-623 (1992) https://doi.org/10.1016/S0040-4020(01)88122-9
  3. Chatis, P. A. and Crumpacker, C. S., Resistance of herpesvirus to antiviral drugs. Antimicrob. Agents Chemother., 36, 1589-1595 (1992) https://doi.org/10.1128/AAC.36.8.1589
  4. Daiz, Y., Bravo, F., and Castillon, S., Synthesis of purine and pyrimidine isodideoxynucleosides from (S)-glycydol using iodoetherification as key step. synthesis of (S, S)-iso-ddA. J. Org. Chem., 64, 6508-6511 (1999) https://doi.org/10.1021/jo990495e
  5. 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 Krenisky, T. A., 1592U89, A novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity. Antimicrob. Agents Chemother., 41, 1082-1093 (1997)
  6. Dias, E. L., Nguyun, S. T., and Grubbs, R. H., Well-defined Ruthenium olefin metathesis catalysts: Mechanism and activity. J. Am. Chem. Soc., 119, 3887-3897 (1997) https://doi.org/10.1021/ja963136z
  7. Herdewijn, P., De Clercq, E., Balzarini, J., and Vanderhaeghe, H., Synthesis and antiviral activity of the carbocyclic analogues of (E)-5-(2-halovinyl)-2'-deoxyuridine and (E)-5-(2-halovinyl)-2'-deoxycytidines. J. Med. Chem., 28, 550-555 (1985) https://doi.org/10.1021/jm50001a003
  8. Jenny, T. F., Horlacher, J., Previsani, N., and Benner, S., Carbocyclic analogs of nucleosides. Part 2. Synthesis of 2',3'-dideoxy-5'-homonucleoside analogs. Helv. Chim. Acta, 75, 1944-1954 (1992) https://doi.org/10.1002/hlca.19920750620
  9. 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
  10. Kitano, K., Miura, S., Ohrui, H., and Meguro, H., Synthesis of 4'-C-fluoromethylnucleosides as potential antineoplastic agents. Tetrahedron, 53, 13315-13322 (1997) https://doi.org/10.1016/S0040-4020(97)00844-2
  11. Ko, O. H. and Hong, J. H., Efficient synthesis of novel carbo-cyclic nucleosides via sequential Claisen rearrangement and ring-closing metathesis. Tetrahedron Lett., 43, 6399-6402 (2002) https://doi.org/10.1016/S0040-4039(02)01384-9
  12. Parker, W: B. and Cheng, Y. C., Mitochondrial toxicity of antiviral nucleoside analogues. J. NIH Res., 6, 57-61 (1994)
  13. Schwab, P., Grubbs, R. H., and Ziller, J. W., Synthesis and application of $RuCl_2(=CHR')(PR_3)_2$: The influence of the alkylidene moiety on metathesis activity. J. Am. Chem. Soc., 118, 100-110 (1996) https://doi.org/10.1021/ja952676d
  14. Roy, A. and Schneller, S. W., 4'-, 1'-Methyl SUbstituted 5'-norcarbanucleosides. J. Org. Chem., 68, 9269-9273 (2003) https://doi.org/10.1021/jo030238g
  15. Youssefyeh, R. D., Verheyden, J. H. P., and Moffatt, J. G., 4'-Substituted nucleosides. Hydroxymethylation of nucleoside 5'-aldehyde. J. Org. Chem., 44, 1301-1309 (1979) https://doi.org/10.1021/jo01322a024
  16. Wachmeister, J., Classon, B., and Samuelsson, B., Synthesis of 2' ,3'-dideoxycyclo-2'-pentenyl-3'-C-hydroxymethyl carbo-cyclic nucleoside analogues as potential anti-viral agents. Tetrahedron, 51, 2029-2038 (1995) https://doi.org/10.1016/0040-4020(94)01067-A