2'-Deoxy-2'-alkoxyaminouridines: Novel 2'-substituted uridines prepared by intramolecular nucleophilic ring opening of 2,2'-O-anhydrouridines

Tetrahedron

Volumn 52, Issue 46, 1996, Pages 14385-14402

  Sebesta, David P ^a   O'Rourke, Sarah S ^a   Martinez, Rogelio L ^a   Pieken, Wolfgang A ^a   McGee, Danny P C ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

URIDINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; PRIORITY JOURNAL; REACTION ANALYSIS;

EID: 0030580438     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4020(96)00870-8     Document Type: Article

References (39)

1. 1. For recent reviews of nucleoside chemistry, modified nucleosides in oligonucleotide synthesis, and naturally occuring modified nucleosides, see: (a) Huryn, D. M.; Okabe, M. Chem. Rev. 1992, 92, 1745-1768.
2. (b) Eaton, B.E.; Pieken, W.A. Ann. Rev. Biochem. 1995, 64, 837-863.
3. (c) Limbach, P. A.; Crain, P. F.; McClosky, J. A. Nucleic Acids Res. 1994, 22, 2183-2196.
4. 2. Aurup, H.; Williams, D. M.; Eckstein, F. Biochemistry 1992, 31, 9636-9641.
5. 3. (a) Tuerk, C.; Gold, L. Science 1990, 249, 505-510.
6. (b) Lin, Y.; Qiu, Q.; Gill, S. C.; Jayasena, S. D. Nucleic Acid Res. 1994, 22, 5229-5234.
7. 4. (a) McGee, D. P. C.; Sebesta, D. P.; O'Rourke, S. S.; Martinez, R. L.; Jung, M. E.; and Pieken, W. A. Tetrahedron Lett. 1996, 37, 1995-1998.
8. (b) see also McGee, D.P.C.; Vaughn-Settle, A.; Vargeese, C.; Zhai, Y. J. Org. Chem. 1996, 61, 781-785.
9. 5. The incorporation of these monomers into synthetic oligonucleotides will be described elsewhere.
10. 6. For examples of intermolecular nucleophilic anhydronucleoside openings, see: (a) Verheyden, J. P. H.; Wagner, D.; Moffatt, J. G. J. Org. Chem. 1971, 36, 250-254.
11. (b) Kirschenheuter, G.; Zhai, Y.; Pieken, W. A. Tetrahedron Lett. 1994, 35, 8517-8520.
12. (c) Xi, Z.; Agback, P.; Plavec, J.; Sandström, A.; Chattopadhyaya, J. Tetrahedron 1992, 48, 349-370.
13. See also: (d) Miller, N.; Fox, J. J. J. Org. Chem. 1964, 29, 1772-1776.
14. (e) Glinski, R. P.; Khan, M. S.; Kalamas, R. L.; Sporn, M. B. J. Org. Chem. 1973, 38, 4299-4305.
15. (f) Mengel, R.; Guschlbauer, W. Angew. Chem. Int. Ed. Engl. 1978, 17, 525.
16. 7. Switzer, C. Y.; Moroney, S. E.; Benner, S. A. Biochemistry, 1993, 32, 10489-10496.
17. 8. Nucleophilic attack at the 2-position by oxygen nucleophiles is likewise well documented, see: (a) Codington, J. F.; Fecher, R.; Fox, J. J. J. Org. Chem. 1962, 27, 163-167.
18. 9. As discussed in reference 4a, we view the anhydronucleoside ring system as an analogue of the allylic alcohol epoxide, substrates which have enjoyed considerable attention as synthetic intermediates. For examples of hydroxyl-tethered nucleophilic opening of such epoxy alcohols, see: (a) Jacobsen, S. Acta Chem Scand. Ser. B, 1988, B42, 605-613
19. (b) Roush, W. R.; Follows, B. C. Tetrahedron Lett. 1994, 35, 4935-4938.
20. See also: (c) Knapp, S.; Kukkola, P. J.; Sharma, S.; Pietranico, S. Tetrahedron Lett. 1987,28, 5399-5402.
21. (d) Bernet, B.; Vasella, A. Tetrahedron Lett. 1983, 24, 5491-5494.
22. (e) Chong, J. M.; Sharpless, K. B. J. Org. Chem. 1985, 50, 1560-1564.
23. (f) Johnson, M. R.; Nakata, T.; Kishi, Y. Tetrahedron Lett. 1979, 20, 4343-4346.
24. (g) Caron, M.; Sharpless, K. B. J. Org. Chem. 1985, 50, 1557-1560.
25. (h) Roush, W. R.; Gustin, D. Tetrahedron Lett. 1994, 35, 4931-4934.
26. 10. Reduction of 2′-oxime derivatives of uridine has been reported, however this approach affords primarily 2′-hydroxylaminouridines of the arabino configuration. See, Tronchet, J. M. J.; Benhamza, R.; Bernardinelli, G.; Geoffroy, M. Tetrahedron Lett., 1990, 31, 531-534.
27. 11. For a discussion of the α-effect, see: England, W. B.; Kovacic, P.; Hanrahan, S. M.; Jones, M. B. J. Org. Chem., 1980, 45, 2057-2063.
28. 12. 5-Iodocytidine: Meisenheimer, K. M.; Meisenheimer, P. L.; Willis, M. C.; Koch, T. H. Nucleic Acids Research, 1996, 24, 981-982. 5-Bromo-2′-deoxyuridine: Hicke, B. H.; Willis, M. C.; Koch, T. H.; Cech, T. R. Biochemistry, 1994, 33, 3364-3373. 5-Iodouridine: Willis, M. C.; Hicke, B. H.; Uhlenbeck, O. C.; Cech, T. R.; Koch, T. H. Science, 1993, 262, 1255-1257.
29. 12. 5-Iodocytidine: Meisenheimer, K. M.; Meisenheimer, P. L.; Willis, M. C.; Koch, T. H. Nucleic Acids Research, 1996, 24, 981-982. 5-Bromo-2′-deoxyuridine: Hicke, B. H.; Willis, M. C.; Koch, T. H.; Cech, T. R. Biochemistry, 1994, 33, 3364-3373. 5-Iodouridine: Willis, M. C.; Hicke, B. H.; Uhlenbeck, O. C.; Cech, T. R.; Koch, T. H. Science, 1993, 262, 1255-1257.
30. 12. 5-Iodocytidine: Meisenheimer, K. M.; Meisenheimer, P. L.; Willis, M. C.; Koch, T. H. Nucleic Acids Research, 1996, 24, 981-982. 5-Bromo-2′-deoxyuridine: Hicke, B. H.; Willis, M. C.; Koch, T. H.; Cech, T. R. Biochemistry, 1994, 33, 3364-3373. 5-Iodouridine: Willis, M. C.; Hicke, B. H.; Uhlenbeck, O. C.; Cech, T. R.; Koch, T. H. Science, 1993, 262, 1255-1257.
31. 13. (a) Sonogashira, K.; Tohda, Y., Hagihara, N. Tetrahedron Lett. 1975, 16, 4467-4470.
32. (b) Hobbs, F. W. Jr. J. Org. Chem. 1989, 54, 3420-3422.
33. 14. (a) Crouch, G. J.; Eaton, B. E. Nucleosides &Nucleotides 1994, 13, 939-944.
34. (b) Dewey, T. M.; Mundt, A. A.; Crouch, G. J.; Zyzniewski, M. C.; Eaton, B. E. J. Amer. Chem. Soc. 1995, 117, 8474-8475.
35. 15. Milder conditions, such as a Mitsunobu reaction (see: (a) Czernecki, S.; Ezzitouni, A. J. Org. Chem., 1992, 57, 7325-7328.
36. (b) Chern, J.-W.; Kuo, C.-C.; Chang, M.-J.; Liu, L.-T. Nucleosides & Nucleotides, 1993, 12(9), 941-949.) have been employed in the synthesis of anhydronucleosides and though these conditions might be compatible with the formation of the 5-iodoanhydrouridine, to afford the desired dehydrated substrate (the 2,2′-anhydro vs. the 2,5′-derivative), protection/ deprotection steps would likely be required. For these reasons, we chose first to evaluate the 5-bromo derivative which was formed by direct analogy to the parent anhydrouridine nucleoside under conditions selective for the formation of the desired 2,2′-derivative.
37. 16. Sebesta, D. P.; O'Rourke, S. S.; Pieken, W. A. J. Org. Chem. 1996, 61, 361-362
38. 17. Rougny, A.; Daudon, M. Bull. Soc. Chim. France, 1976, 833-838.
39. 8N; C, 71.23; H, 5.98; N, 2.25. Found: C, 70.96; H, 6.09; N, 2.22.