Azido-(amino-)furanosyl nucleosides and their phosphoramidates

Abstract

The ring-opening of 2,2′-anhydro-1 -[5-azido-5 and 5-benzamido-3 5-deoxy-3-O-methylsulfonyl-β-D-arabinofuranosyl]uracil by the ion exchanger Dowex 50 (H⁺) afforded the corresponding1 -[5-azido-8 and 5-benzamido-12 5-deoxy-3-O-methylsulfonyl-β-D-arabinofuranosyl]uracil. Hydrogenolysis of the azido nucleosides over Pd-black in the presence of benzoic acid anhydride led to the corresponding benzamido nucleosides in high yields. The 5′-azido-2′,3′-oxirane 10 on reaction with ethanolic ammonia generated 1-(3-amino-5-azido-3,5-dideoxy-β-D-arabinofuranosyl)uracil 15 and 1 -(2-amino-5-azido-2,5-dideoxy-β-D-xylofuranosyl)uracil 16 in a ratio 2:1. The 5′-O-mesyl-2′,3′-oxirane 25, on being treated with NaN₃ in DMF at 100 °C, afforded 2′,5′-anhydro-1-(3-azido-3-deoxy-β-D-arabino-furanosyl)uracil 26(54.5%), 3′,5′-diazido-β-D-arabinofuranosy 27(20.6%) and 2′,5′-diazido-β-D-xylo-furanosyl 28(5.4%). The hydrogenolysis of 5 over Pd-black proceeded into 2,5′-imino-1-(3-O-methyl-sulfonyl-β-D-arabinofuranosyl)uracil 32 which, as the 5′-benzamido derivative 36, was transformed into 3. The 5′-azido compound 5 and 10 on reaction with triphenyl phosphite in aqueous dioxane gave the respective 5′-diphenylphosphoramidate 38 and 39. Similarly, the 3′-azido compound 22 was converted into 3′-diphenylphosphoramidate 40.