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

2,3,4-Tri-O-acetyl-5-thio-alpha-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 alpha,beta-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 alpha,beta-ratio of 15:85. Deacetylation of 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 alpha-anomers are in the C-4(1) conformation and the beta-anomers in the C-1(4). Both anomeric thioglycosides were present in their C-4(1) conformation. (C) 1997 Elsevier Science Ltd.