M. Zhong, M. J. Robins / Tetrahedron Letters 44 (2003) 9327–9330
9329
Scheme 1.
glucose penta-acetate and 5b proceeded at a slower rate
to give the N9 product in reasonable yield (68%).
Attempted coupling of 5b with the 2-N-acetyl (6b) or
trifluoroacetyl (6a) derivatives of 1,3,4,6-tetra-O-acetyl-
7. Robins, M. J.; Zou, R.; Hansske, F.; Madej, D.; Tyrrell,
D. L. J. Nucleosides Nucleotides 1989, 8, 725–741.
8. Robins, M. J.; Zou, R.; Guo, Z.; Wnuk, S. F. J. Org.
Chem. 1996, 61, 9207–9212.
9. Robins, M. J.; Sarker, S.; Wnuk, S. F. Nucleosides Nucleo-
tides 1998, 17, 785–790.
2-amino-2-deoxy-b-D-glucopyranose gave complex mix-
tures with extensive decomposition of 5. The
1-O-acetyl-N-phthaloyl derivative 6c did not function
well, but the more reactive 1-trichloroacetimidate 6d
was coupled with 5b to give the N9 glycosyl isomer 8 in
moderate yield (54%). Treatment of 8 with methanolic
ammonia gave 9-[2-N-(2-carboxamidobenzoyl)amino-2-
10. Zou, R.; Robins, M. J. Can. J. Chem. 1987, 65, 1436–
1437.
11. See: (a) Cheung, A. W.-H.; Sidduri, A.; Garofalo, L. M.;
Goodnow, R. A., Jr. Tetrahedron Lett. 2000, 41, 3303–
3307 and the discussion and references therein; (b) Zhu,
W.; Gumina, G.; Schinazi, R. F.; Chu, C. K. Tetrahedron
2003, 59, 6423–6431.
12. Assignments of N9 versus N7 isomers can be made
readily from the 13C NMR shifts of peaks for C5, C6,
and C8. Signals for these three carbon atoms were imbed-
ded within ranges for N9 isomers, and cleanly separated
from ranges for N7 compounds.6–8
deoxy-b- -glucopyranosyl]guanine (9). Thus, 2-N-ace-
D
tyl-6-O-diphenylcarbamoylguanine (5a) is a very useful
derivative of guanine for Lewis acid-catalyzed regiospe-
cific N9 coupling with active glycosyl donors derived
from
1,2,3,5-tetra-O-acylpentofuranoses
or
a-
haloethers. However, 5b does not couple readily with
weak glycosyl donors, and it is susceptible to cleavage
of the DPC group. The resulting 2-N-acetylguanine
couples at both N7 and N9, as in the V–K–B method.
13. Lemieux, R. U.; Takeda, T.; Chung, B. Y. In Synthetic
Methods for Carbohydrates; El Khadem, H. S., Ed.; ACS
Symposium Series: Washington, DC, 1976; Vol. 39, pp.
90–115.
Acknowledgements
14. (a) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem.
Biochem. 1994, 50, 21–123; (b) Schmidt, R. R.; Jung,
K.-H. In Preparative Carbohydrate Chemistry; Hanes-
sian, S., Ed.; Marcel Dekker: New York, 1997; pp.
283–312.
Generous donations of pharmaceutical company gift
funds are greatly appreciated. M.Z. is the recipient of
an R. K. Robins Graduate Research Fellowship from
Brigham Young University.
15. Kretzschmar, G.; Stahl, W. Tetrahedron 1998, 54, 6341–
6358.
16. 9-[2-N-(2-Carboxamidobenzoyl)amino-2-deoxy-b-D-gluco-
References
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(CH2Cl2MeOH/CH2Cl2, 1:1801:90) to give 8 (453
mg, 54%) as a white foam: HRMS (FAB) m/z 828.2258
(MNa+ [C40H35O12N7Na]=828.2241).
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