Synthesis of 4-cyano- and 4-nitrophenyl 2,5-anhydro-1,6-dithio-α-d-gluco- and -α-l-guloseptanosides carrying different substituents at C-3 and C-4 Original Research Article

Treatment of 1,6:2,5-dianhydro-3,4-di-O-methanesulfonyl-1-thio-d-glucitol in methanol with sodium hydroxide afforded 1,6:2,5:3,4-trianhydro-1-thio-allitol, 1,4:2,5-dianhydro-6-methoxy-1-thio-d-galactitol, 1,6:2,5-dianhydro-4-O-methyl-1-thio-d-glucitol, 1,6:2,5-dianhydro-3-O-methanesulfonyl-1-thio-d-glucitol and 1,6:2,5-dianhydro-4-deoxy-1-thio-d-erythro-hex-3-ulose (14) in 5, 4, 28, 5.5 and 41% yield, respectively. Formation of these derivatives can be explained via a common sulfonium intermediate. Reduction of 14 with sodium borohydride and subsequent acetylation afforded 3-O-acetyl-1,6:2,5-dianhydro-4-deoxy-1-thio-d-xylo-hexitol, the absolute configuration of which was proved by X-ray crystallography. The 1,6:2,5-dianhydro-1-thio-d-hexitol derivatives in which the free OH groups were protected by acetylation, methylation or mesylation were converted by a Pummerer reaction of their sulfoxides into the corresponding 1-O-acetyl hexoseptanose derivatives which were used as donors for the glycosidation of 4-cyano- and 4-nitrobenzenethiol, respectively. The Pummerer reaction of 1,6:2,5-dianhydro-4-deoxy-3-O-methyl-1-thio-d-xylo-hexitol S-oxide gave, besides 1-O-acetyl-2,5-anhydro-3-deoxy-4-O-methyl-6-thio-α-l- (23) and 1-O-acetyl-2,5-anhydro-4-deoxy-3-O-methyl-6-thio-α-d-xylo-hexoseptanose (25), 1-O-acetyl-4-deoxy-2,6-thioanhydro-d-lyxo-hexopyranose, formed in a rearrangement reaction. The same rearrangement took place, when a mixture of 23 and 25 was used as donor in the glycosidation reaction with 4-cyanobenzenethiol, applying trimethylsilyl triflate as promoter. The oral antithrombotic activity of the obtained α-thioglycosides was determined in rats, using Pescadorʹs model.