Synthesis of β-D-ribofuranosylbenzazoles using nitrile oxide addition chemistry

A nitrile oxide based route to 2-beta-D-ribofuranosylbenzazoles has been developed. Tri-O-benzoyl-beta-D-ribofuranosylformonitrile oxide (14) was generated from the corresponding carbaldoxime 16 by treatment with NCS/pyridine, followed by base-induced dehydrochlorination of the resulting hydroximoyl chloride. Reaction of the nitrile oxide with 1,2-diaminobenzene afforded 2-(tri-O-benzoyl-beta-D-ribofuranosyl)benzimidazole (21), from which 2-(beta-D-ribofuranosyl) benzimidazole (22) was prepared by treatment with Et3N/MeOH. 2-Aminophenol reacted similarly to yield 2-(tri-O-benzoyl-beta-D-ribofuranosyl) benzoxazole (18). In the absence of a co-reactant dimerisation of the nitrile oxide afforded 3,4-di(tri-O-benzoyl-beta-D-ribofuranosyl)-1,2,5-oxadiazole-2-oxide (17). The carbaldoxime starting material 16 was prepared from tri-O-benzoyl-beta-D-ribofuranosyl cyanide by reaction with semicarbazide to form the semicarbazone, followed by transimination with hydroxylamine.