Synthesis of 4-substituted phenyl 3,6-anhydro-1,3-dithio-d-glucofuranosides and -pyranosides as well as 2,6-anhydro-1,2-dithio-α-d-altrofuranosides possessing antithrombotic activity Original Research Article

1,2,5-Tri-O-acetyl-3,6-anhydro-3-thio-d-glucofuranose was synthesised starting from d-glucose and was used as a donor for the glycosidation of 4-cyano- and 4-nitrobenzenethiol. In the latter reaction, besides an anomeric mixture of the 4-nitrophenyl 2,5-di-O-acetyl-3,6-anhydro-1,3-dithio-d-glucofuranosides, the corresponding 2,6-anhydro-1,2-dithio-d-altrofuranosides were also obtained, formed via a rearrangement of the sugar moiety. A similar rearrangement could be observed during the hydrolysis of the glycosidic bond of methyl 3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-α-d-glucopyranoside with aqueous trifluoroacetic acid, affording after acetylation besides 1-O-acetyl-3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-α-d-glucopyranose (32α), 1,1,5-tri-O-acetyl-3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-d-glucose, methyl 3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-β-d-glucopyranoside and 1,5-di-O-acetyl-2,6-anhydro-3-O-(4-nitrobenzoyl)-2-thio-α-d-altrofuranose (40). Glycosidation of 4-cyanobenzethiol with 32α in the presence of trimethylsilyl triflate as promoter afforded 4-cyanophenyl 3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-1,3-dithio-β-d-glucopyranoside as a minor component only, besides 4-cyanophenyl 3,6-anhydro-2-S-(4-cyanophenyl)-4-O-(4-nitrobenzoyl)-1,2,3-trithio-β-d-glucopyranoside. When boron trifluoride etherate was used as promoter in the reaction of 32α with 4-cyano- and 4-nitrobenzenethiol, the corresponding β-thioglycosides were obtained, while 40 gave under identical conditions the α anomers exclusively. All thioglycosides obtained after deacylation were submitted to biological evaluation. Among these glycosides, the 4-cyanophenyl 3,6-thioanhydro-1,3-dithio-d-glucofuranoside possessed the strongest oral antithrombotic effect.