Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-l- and -d-arabinopyranosides possessing antithrombotic activity

5-S-Benzoyl-2,3-O-isopropylidene-5-thio-l-arabinose, prepared from l-arabinose diethyl dithioacetal gave, on treatment with sodium methoxide in methanol, 4-O-benzoyl-2,3-O-isopropylidene-5-thio-l-arabinopyranose 12 which was converted into its 1-O-acetate 14. Hydrolysis of 12 in acetic acid–water afforded, after acetylation, 1,2,3-tri-O-acetyl-4-O-benzoyl-5-thio-l-arabinopyranose 17 which was transformed into 2,3-di-O-acetyl-4-O-benzoyl-5-thio-l-arabinopyranosyl bromide 20. Zemplén deacylation of 17 gave 5-thio-l-arabinopyranose which was converted via 1,2,3,4-tetra-O-acetyl-5-thio-β-l-arabinopyranose 5 into 2,3,4-tri-O-acetyl-5-thio-β-l-arabinopyranosyl bromide 6 and into O-(2,3,4-tri-O-acetyl-5-thio-l-arabinopyranosyl) trichloro-acetimidate 7. Glycosidation of 4-nitrophenol with 12 under the Mitsunobu conditions afforded 4-nitrophenyl 4-O-benzoyl-2,3-O-isopropylidene-5-thio-α- and β-l-arabinopyranoside in a ∼1:2 ratio. Condensation of the glycosyl donors 6, 7, 17, and 20 with 4-cyano- and 4-nitrobenzenethiol yielded, after deacylation, 4-cyano- and 4-nitrophenyl 1,5-dithio-α- and β-l-arabinopyranosides 28α, 28β, 29α and 29β in different ratios and yields, depending on the reaction conditions applied. In a similar manner the corresponding d-isomers 30α, 30β, 31α and 31β were also prepared. All of these glycosides, except 28α, showed a stronger oral antithrombotic effect in rats as compared to beciparcil, used as reference.