Synthesis of 4-cyanophenyl 2-azido-2-deoxy- and 3-azido-3-deoxy-1,5-dithio-β-D-xylopyranosides

Article abstract of DOI:10.1016/S0008-6215(97)00079-7

Azidonitration of 3,4-di-O-benzoyl-1,5-anhydro-5-thio-D-threo-pent-1-enitol (3,4-di-O-benzoyl-5-thio-D-xylal) afforded a 1:1 mixture of 2-azido-3,4-di-O-benzoyl-2-deoxy-1-O-nitro-5- thio-α-D-xylo- and lyxo-pyranosides, which were converted after separation into their 1-O-acetyl derivatives 8 and 11, respectively. Glycosidation of 8 and 11 with methanol in the presence of trimethylsilyl triflate afforded methyl 2-azido-3,4-di-O-benzoyl-2-deoxy-5-thio-α,β-D-xylo- and lyxo-pyranosides in a ratio of 1:1, and 5:2, respectively. When 4-cyanothiophenol was used as acceptor for the glycosidation of 8, the anomeric thioglycosides were formed in the same ratio (1:1). Deacetylation of the β-isomer afforded 4-cyanophenyl 2-azido-2-deoxy-1,5-dithio-β-D-xylopyranoside 3. 3-Azido-3-deoxy-5-S-benzoyl-1,2-O-isopropylidene-α-D-xylofuranose was synthesised from D-glucose in 10 steps and was converted into 1,2,4-tri-O-acetyl-3-azido-3-deoxy-5-thio-D-xyloperanose 31. Glycosidation of 31 with 4-cyanothiophenol in the presence of trimethylsilyl triflate afforded 4-cyanothiophenyl 2,4-di-O-acetyl-3-azido-3-deoxy-5-thio-α, β-D-xylopyranoside in a ratio of 1:1.5. Their deacetylation gave 4-cyanophenyl 3-azido-3-deoxy-1,5-dithio-β-D-xylopyranoside 4 and its α-anomer 34. Reduction of 4 with sodium borohydride-nickel chloride gave the 3-amino derivative 36, which was converted into the acetamido compound 38. Compounds 3, 4, and 36 possess high oral antithrombotic activity, which decreases on acetylation of the amino group in 38. The α-anomer 34 was inactive.