Synthesis of 9-(4-thioxylofuranosyl)adenine via a novel glycosylation reaction

Tetrahedron Letters

Volumn 39, Issue 3-4, 1998, Pages 205-208

  Hartsel, Stephanie A ^a   Marshall, William S ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

9 (4 THIOXYLOFURANOSYL)ADENINE; ADENINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; GLYCOSYLATION; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0032518775     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)10526-3     Document Type: Article

References (10)

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2. 2. Dyson, M. R.; Coe, P. L.; Walker, R. T. Nucleic Acids Res. Symp. Series. 1991, 24, 1-4.
3. 3. Hartsel, S.; Chen, C.; Kennedy, J.; Bendele, A.; Wright, C.; Marshall, W. S. Nucleosides Nucleotides 1997, 16 (in press).
4. 4. Leydier, C.; Bellon, L.; Barascut, J. L.; Deydier, J.; Georges, M.; Helene, P.; Moulay, A. E. A.; Imbach, J. L. Nucleosides Nucleotides 1994,13 , 2035-2050.
5. 5. Tiwari, K. N.; Secrist, J. A.; Montgomery, J. A. Nucleosides Nucleotides. 1994, 13 , 1819-1828.
6. 6. Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. Tetrahedron Letters. 1990 34 , 1331-1334.
7. 7. Bellon, L.; Barascut, J. L., Imbach, J. L. Nucleosides Nucleotides 1992, 11, 1467-1479.
8. 8. An inversion of configuration at the 4 position was necessary to attain the D-xylo isomer after ring closure. This was achieved through a Mitsunobu inversion reaction. We found the reaction proceeds more efficiently when the solvent employed was benzene, rather than the commonly reported THF. The diethylazodicarboxylate (DEAD) was replaced by the more reactive diisopropylazodicarboxylate (DIAD). The DIAD (1.5 eq) was added dropwise over five minutes to a mixture of 2,3,5-tri-O-benzyl-xylose-1-dithiobenzylacetal (0.357 mmol, 0.181 g), and 1.5 equivalents of both p-nitrobenzoic acid and triphenylphosphene under nitrogen in a vessel protected from light. Formation of the product was monitored by tlc and the product was purified by silica gel chromatography using hexane:ethyl acetate (5:1).
9. 3OH (1:2) before injection. A gradient of 0 - 70% methanol over 30 minutes was found to be effective in separating the isomers. The β isomer eluted at 18.8 minutes and the a isomer at 20.02 minutes.
10. 3OD) δ 6.16 (d, H, H1′). 2D data not shown.