A concise synthesis of 3-fluoro-5-thio-xylo- and glucopyranoses, useful precursors towards their corresponding pyranonucleoside derivatives

作者：Tsoukala Evangelia; Manta Stella; Tzioumaki Niki; Agelis George; Komiotis Dimitri^*

来源：Carbohydrate Research, 2008, 343(6): 1099-1103.

DOI：10.1016/j.carres.2008.02.004

• thiosugars
• thionucleosides
• 3-fluoro-5-thioxylopyranose
• 3-fluoro-5-thio-glucopyranose
• thymine

The chemical synthesis of 1,2,4-tri-O-acetyl-3-deoxy-3-fluoro-5-thio-D-xylopyranose, 1,2,4,6-tetra-O-acetyl-3-deoxy-3 -fluoro-5-thio-alpha(-D-glucopyranose and their corresponding nucleosides of thymine is described. Treatment of 3-fluoro-5-S-acetyl-5-thio-D-xylofuranose, obtained by hydrolysis of the isopropylidene group of 3-fluoro-1,2-O-isopropylidene-5-S-acetyl-5-thio-D-xylofuranose, with methanolic ammonia and direct acetylation, led to triacetylated 3-deoxy-3-fluoro-5-thio-D-xylopyranose. Condensation of acetylated 3-fluoro-5-thio-D-xylopyranose with silylated thymine afforded the corresponding nucleoside. Selective benzoylation and direct methanesulfonylation of 3-fluoro-1,2-O-isopropylidene-alpha-D-glucofuranose gave the 6-O-benzoyl-5-O-methylsulfonyl derivative, which on treatment with sodium methoxide afforded the 5,6-anhydro derivative. Treatment of the latter with thiourea, followed by acetolysis, gave the 3-fluoro-5-S-acetyl-6-O-acetyl-1,2-O-isopropylidene-5-thio-alpha-D-glucofuranose. 3-Fluoro-5-S-acetyl-6-O-acetyl-5-thio-D-glucofuranose, obtained after hydrolysis of 5-thiofuranose isopropylidene, was treated with ammonia in methanol and directly acetylated, giving tetraacetylated 3-deoxy-3-fluoro-5-thio-alpha-D-glucopyranose. Condensation of the latter with silylated thymine afforded the desired 3-deoxy-3-fluoro-5-thio-beta-D-glucopyranonucleoside analogue.

• 出版日期2008-5-5