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-b-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-b-D-glucopyranosylthymine derivative 13, which furnished the 3-azido-3-deoxy-b-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.

Synthesis and Anti-HIV Activity of 4′-Substituted 4′-Thiothymidines: A New Entry Based on Nucleophilic Substitution of the 4′-Acetoxy Group

“…The other two products were the ring-expanded compounds 15 (34%) and 16 (15%), their thiopyranosyl structures being evident from the observed HMBC correlations between H-5′ and C-1′. 11 A plausible reaction mechanism for the formation of these products is depicted in Scheme 4.…”

S-Ribosylhomocysteine analogs containing a [4-thio]ribose ring

“…Presumably the mesylated thiosugar underwent a rearrangement reaction into the thiopyranoses through an episulfonium ion intermediates. 36 To avoid such ring enlargement, thioether 5 was first oxidized to sulfoxide 6 with 3-chloroperbenzoic acid ( m -CPBA). Interestingly, sulfoxide 6 was obtained in 94% yield as a single diastereoisomer, 37 whose stereochemistry was tentatively assigned as S at sulfur atom.…”

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

“…Inspired by the notable outcomes of triazolyl glycohybrids as anticancer or antiproliferative compounds, Al-Masoudi and co-workers designed a novel family of 5-thio- altro -isonucleoside glycohybrids, 1060 , synthesized via cycloaddition of clickable azido thiosugar 1059 with well-equipped alkyne functionality under heating conditions in toluene in significant yield (Scheme ). Utilizing the regio-isomerism, glycohybrid 1061 was synthesized. However, the report lacks pharmacological or toxicological assays, and thus, further investigation is needed for pharmacophore consideration.…”