title: Synthesis of 4-cyanophenyl and 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-beta-D-arabino- and -beta-D-lyxopyranosides possessing antithrombotic activity.
abstract: Tri-O-acetyl-5-thio-D-ribopyranosyl bromide was converted into 3,4-di-O-benzoyl-1,5-anhydro-5-thio-D-erythro-pent-1-enitol (3,4-di-O-benzoyl-5-thio-D-ribal), the azidonitration of which afforded an unstable mixture of 2-azido-3,4-di-O-benzoyl-2-deoxy-1-O-nitro-5-thio-D-pentopyranoside++ + isomers. This was converted without separation into the corresponding 1-O-acetyl derivatives from which an alpha,beta anomeric mixture of the 1-O-acetyl-2-azido-3,4-di-O-benzoyl-2-deoxy-5-thio-D-arabinopyranose+ ++ isomers could be isolated in high yield. Glycosidation of this mixture with 4-cyano- or 4-nitrobenzenethiol, using trimethylsilyl triflate or boron trifluoride etherate, respectively, as promoters gave the corresponding D anomers exclusively. Zemplén debenzoylation afforded 4-cyanophenyl as well as 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-beta-D-arabinopyranoside, respectively. When 1-O-acetyl-2-azido-3,4-di-O-benzoyl-2-deoxy-5-thio-D-lyxopyranose was used as glycosyl donor only the corresponding 1 anomers, i.e., 4-cyanophenyl as well as 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-beta-D-lyxopyranosides, could be isolated after Zemplén debenzoylation in high yield. All four 1,5-dithioglycosides possess significant oral antithrombotic activity.
authors.affiliation: Institute for Drug Research, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Bozó
authors.forename: J
authors.initials: J
authors.lastname: Kuszmann
mesh_terms: D000818:Animals; D001089:Arabinose / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D010429:Pentoses / Q000138:chemical synthesis*; D051381:Rats; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D005343:Fibrinolytic Agents; D010429:Pentoses; D013865:Thioglycosides; C043333:lyxose; D001089:Arabinose