Synthesis of novel NH-1,2,3-triazolo-nucleosides by the Banert cascade reaction

Nucleoside analogs with the 4,5-dimethyl-NH-1,2,3-triazolo-linker between thymine and a carbohydrate, or a hydroxyalkoxyl, or phosphonomethoxyl residue, were obtained by the Bannert cascade reaction from 1-(4-azidobut-2-yn-1-yl)thymine and the carbohydrate or acyclic alcohol. The reaction conditions were developed on the basis of a thermal analysis of the starting azide and by the optimization of the reaction components ratio. The best results were obtained when the reaction cascade employed the azide/nucleophile molar ratio of 1/14, at 55 °C, with no solvent addition. The reaction showed good discrimination between the pentofuranose hydroxyls, yielding triazoles linked at the carbohydrate 5′-oxygen atom.