Synthesis of 4-cyanophenyl and 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-β-d-arabino- and -β-d-lyxopyranosides possessing antithrombotic activity

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 α,β 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 β anomers exclusively. Zemplén debenzoylation afforded 4-cyanophenyl as well as 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-β-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 β anomers, i.e., 4-cyanophenyl as well as 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-β-d-lyxopyranosides, could be isolated after Zemplén debenzoylation in high yield. All four 1,5-dithioglycosides possess significant oral antithrombotic activity.