Thiosugar Nucleosides. Effect of Sulfur in the Synthesis of Substituted Azido‐5‐Thio‐D‐Gluco‐ and Allopyranosyl‐N‐Nucleosides and New Isothionucleoside Derivatives Thereof

Abstract

1‐(2,3,4‐tri‐O‐acety‐6‐azido‐6‐deoxy‐5‐thio‐β‐D‐glucopyranosyl)thymine 5 and the 6‐thio‐septanosylthymine analogue 7 were obtained via the intramolecular displacement of the corresponding tosylate 2 by azide. Alternatively, 5 was obtained from bromination of alcohol 1 in the presence of azide. Deblocking of 5 afforded the nucleoside 6. Glycosylation of the tetraacetate 11, obtained by acetolysis of 10 with thymine, afforded the 3‐O‐tosyl‐β‐D‐glucopyranosylthymine derivative 13, which furnished the 3‐azido‐3‐deoxy‐β‐D‐allopyranosyl‐thymine analogue 14 on reaction with azide ion. Alternatively, the glucoside 12 gave the corresponding gluco analogue 16 on treatment with azide. Acetolysis of 16 furnished the tetraacetate 17, which was subjected for glycosylation to give the gluco nucleoside 18. Deblocking of 14 and 18 afforded the free 3‐azido‐nucleosides 15 and 19, respectively. The isothionucleoside 21 was prepared from treatment of thymine with the 2,3‐epoxide derivative 20 in the presence of Ti(i‐PrO)₄ and triethyl amine. Mild acid hydrolysis of 21 afforded 22. Cycloaddition of the 2‐azido‐altroside 23 with dimethyl acetylenedicarboxylate gave the 1,2,3‐triazole derivative 24. Treatment of 24 with methanolic ammonia afforded the 4,5‐carboxamide analogue 25. The conformations of the new products were studied by NMR spectroscopy.

Keywords:

• Biological activity
• Glycosylation
• Epimerization
• Nucleosides
• Isothionucleosides