View PDF Version
 
DOI: 10.1039/A604559F (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1997, 1887-1894

Synthesis of 2-substituted 2′-deoxyguanosines and 6-O-allylguanines via the activation of C-2 by a trifluoromethanesulfonate group

(Note: The full text of this document is currently only available in the PDF Version )

Christine Edwards, Gernot Boche, Thomas Steinbrecher and Susanne Scheer

Abstract

A new general synthesis of 2-substituted 2′-deoxyguanosine and 6-O-allylguanine analogues is reported. 2-O-Trifluoromethylsulfonyl-6-O-allyl-3′,5 ′-bis-O-(tert-butyldimethylsilyl)-2′- deoxyxanthosine 8 can be converted into a 2-substituted 2′-deoxyguanosine analogue by substitution of the triflate (trifluoromethanesulfonate) moiety using a selected nucleophile, followed by deprotection. Therefore, a 2′-deoxyguanosine may overall be converted into a 2-substituted 2′-hypoxanthosine analogue in seven steps. Similar methodology has been used to synthesize 2-substituted 6-O-allylguanines which are of particular interest as potential resistance-modifying agents in cancer chemotherapy.

References

  1. R. Vince and M. Hua, J. Med. Chem., 1990, 33, 17 CrossRef CAS.
  2. H. J. Schaeffer, L. Beauchamp, P. de Miranda, G. B. Elion, D. J. Bauer and P. Collins, Nature, 1978, 272, 583 CAS.
  3. F. Focher, C. Hildebrand, S. Freese, G. Ciarrocchi, T. Noonan, S. Sangalli, N. Brown, S. Spadari and G. Wright, J. Med. Chem., 1988, 31, 1496 CrossRef CAS.
  4. H. Xu, G. Maga, F. Focher, E. R. Smith, S. Spadari, J. Gambino and G. E. Wright, J. Med. Chem., 1995, 38, 49 CrossRef CAS.
  5. G. E. Wright and L. W. Dudycz, J. Med. Chem., 1984, 27, 175 CrossRef CAS.
  6. G. E. Wright, L. W. Dudycz, Z. Kazimierczuk, N. C. Brown and N. N. Kahn, J. Med. Chem., 1987, 30, 109 CrossRef CAS.
  7. T. Steinbrecher, C. Wameling, F. Oesch and A. Seidel, Angew. Chem., Int. Ed. Engl., 1993, 32, 404 CrossRef.
  8. S. Scheer, T. Steinbrecher and G. Boche, Environ. Health Perspect., 1994, 71, 151.
  9. K. K. Ogilvie, Can. J. Chem., 1973, 51, 3799 CAS.
  10. F. Himmelsbach, B. S. Schulz, T. Trichtinger, R. Charubala and W. Pfleiderer, Tetrahedron, 1984, 40, 59 CrossRef CAS.
  11. O. Mitsunobu, Synthesis, 1981, 1 CrossRef CAS.
  12. C. Temple Jr, M. C. Thorpe, W. C. Coburn Jr and J. A. Montgomery, J. Org. Chem., 1966, 31, 935.
  13. C. Temple Jr, C. L. Kussner and J. A. Montgomery, J. Org. Chem., 1966, 31, 2210.
  14. E. J. Corey and J. W. Suggs, J. Org. Chem., 1973, 38, 3224 CrossRef CAS.
  15. D. B. Ludlum, Mutat. Res., 1990, 233, 117 CrossRef CAS (and references therein).
  16. A. E. Pegg, Cancer Res., 1990, 50, 6119 CAS (and references therein).
  17. A. E. Pegg and T. L. Byers, FASEB J., 1992, 6, 2302 Search PubMed.
  18. M. E. Dolan, K. Morimoto and A. E. Pegg, Cancer Res., 1985, 45, 6413 CAS.
  19. R. C. Moschel, M. G. McDougall, M. E. Dolan, L. Stine and A. E. Pegg, J. Med. Chem., 1992, 35, 4486 CrossRef CAS.
  20. C. E. Arris, C. Bleasdale, A. H. Calvert, N. J. Curtin, C. Dalby, B. T. Golding, R. J. Griffin, J. M. Lunn, G. N. Major and D. R. Newell, Anticancer Drug Design, 1994, 9, 401 Search PubMed.
  21. M.-Y. Chae, M. G. McDougall, M. E. Dolan, K. Swenn, A. E. Pegg and R. C. Moschel, J. Med. Chem., 1994, 37, 342 CrossRef CAS.
  22. C. R. Frihart and N. J. Leonard, J. Am. Chem. Soc., 1973, 95, 7174 CrossRef CAS.
  23. B. R. Baker and P. M. Tanna, J. Org. Chem., 1965, 30, 2857 CAS.
Click here to see how this site uses Cookies. View our privacy policy here.