Synthesis of 4-cyanophenyl 4-azido-4-deoxy-1,5-dithio-β-D-xylopyranoside

Article abstract of DOI:10.1016/S0008-6215(97)00128-6

L-Arabinose diethyl dithioacetal was converted, via its 4-azido-5-S-benzoyl-4-deoxy-2,3-O-isopropylidene-5-thio-D-xylose diethyl dithioacetal, into 4-azido-4-deoxy-5-thio-α-D-xylopyranose triacetate 29. Glycosidation of 29 with 4-cyanothiophenol in the presence of trimethylsilyl triflate gave the 4-cyanophenyl 2,3-di-O-acetyl-4-azido-4-deoxy-1,2-dithio-α- and -β-D-xylopyranosides 31 and 33 as well as 3-O-acetyl-2,5-anhydro-4-azido-4-deoxy-5- thio-D-lyxose bis(4-cyanophenyl) dithioacetal 34 in a 8:2:1 respective ratio. Treatment of 29 with hydrogen bromide in acetic acid yielded a 1:4 mixture of 2,3-di-O-acetyl-4-azido-4-deoxy-5-thio-D-xylopyranosyl bromide 38 and 2,3 -di-O-acetyl-5-bromo-5-deoxy-4-thio-L-arabinofuranosyl bromide 40. Reaction of the mixture of bromides 38 and 40 with 4-cyanothiophenol in the presence of potassium carbonate afforded the expected 31 and 33 only in traces, while 2-(1R,2S,-1,2-di-O-acetyl-1,2-dihydroxy-but-3-en-1-yl)-5-cyano-1,3 dithiole and 4-cyanophenyl 2,3-di-O-acetyl-5-S-(4-cyanophenyl)-1,4,5-trithio-α-L-arabinofuranoside (42) were isolated in 18% and 20% yield, respectively. The formation of these two derivatives is tentatively explained by involvement of a radical reaction mechanism. When O-(2,3-di-O-acetyl-4-azido-4-deoxy-5-thio-α-D-xylopyranosyl) trichloroacetimidate was used as donor and boron trifluoride ethyl etherate as promoter, 31 and 33 were formed in excellent yield (96%) in a 2:1 ratio. The glycosides, obtained on deacetylation of 33, 34, and 42 showed a significant antithrombotic activity on rats.