Synthesis of 4-cyanophenyl 2-deoxy-1,5-dithio-β-D-threo-pentopyranoside

Article abstract of DOI:10.1016/S0008-6215(97)00001-3

2,3,4-Tri-O-acetyl-5-thio-α-D-xylopyranosyl bromide was converted with zinc in the presence of 4-picoline into 3,4-di-O-acetyl-1,5-anhydro-5-thio-D-threo-pent-1-enitol 5. Treatment of 5 with N-iodosuccinimide-water in acetonitrile afforded a mixture which gave, after reduction with sodium borohydride-nickel chloride and subsequent acetylation, only 1,3,4-tri-O-acetyl-2,5-anhydro-5-thio-D-lyxitol. Deacetylation and subsequent benzoylation of 5 gave 3,4-di-O-benzoyl-1,5-anhydro-5-thio-D-threo-pent-1-enitol, the hydrogen bromide addition products of which were treated with sodium 4-cyanobenzenethiolate to give the anomeric mixture of the corresponding thioglycosides in low yield with an α,β-ratio of 3:7. When the mixture of the hydrogen bromide addition products was converted with silver acetate into their 1-O-acetates and condensation with 4-cyanobenzenethiol was performed in the presence of trimethylsilyl triflate, the thioglycosides were obtained in high yield with an α,β-ratio of 15:85. Deacetylation oil this mixture afforded the title compound which showed high oral antithrombotic activity in rats. Conversion of methyl 2-deoxy-5-thio-D-threo-pentofuranoside into 2-deoxy-5-thio-D-threo-pentopyranose triacetate could be carried out in low yield only. Structures, including the conformation of the anomeric acetates and the thioglycosides, were determined by NMR spectroscopy. Because of the anomeric effect of the acetoxy group, the α-anomers are in the ⁴C₁ conformation and the β-anomers in the ¹C₄. Both anomeric thioglycosides were present in their ⁴C₁ conformation.