Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-d-ribopyranosides as well as their 2-deoxy and 2,3-dideoxy derivatives possessing antithrombotic activity

1,2,3,4-Tetra-O-acetyl-5-thio-d-ribopyranose as well as its 1-bromide were used as donors in the reaction with 4-cyano- and 4-nitrobenzenethiol, to give the corresponding thioglycosides in different anomeric ratios depending on the reaction conditions. Zemplén deacetylation afforded 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-α- and β-d-ribopyranosides, respectively. 1,3,4-Tri-O-acetyl-2-deoxy-5-thio-d-erythro-pentopyranose was synthesized from methyl 2-deoxy-d-erythro-pentofuranoside and was coupled with 4-cyano- and 4-nitrobenzenethiol to give anomeric mixtures from which 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-β-d-erythro-pentopyranosides were isolated after deacetylation. 1,4-Di-O-acetyl-2,3-dideoxy-5-thio-d-glycero-pentopyranose was obtained starting from 1,2;5,6-di-O-isopropylidene-d-mannitol and used as the donor in the glycosylation reaction with 4-cyano- and 4-nitrobenzenethiol. The resulting anomeric mixtures were separated to give, after deacetylation, 4-cyanophenyl as well as 4-nitrophenyl 2,3-dideoxy-1,5-dithio-β-d-glycero-pentopyranosides. All of these thioglycosides showed significant antithrombotic activity on rats after oral administration.