Síntese de 1H-1,2,3-triazol glicopiranosídeos análogos de nucleosídeos com potencial atividade antiviral

Abstract

In this work, new nucleoside analogues containing the heterocyclics 1,2,3-triazol and pyrimidine conjugated with glycopyranosides were synthesized. Initially, the construction of our first synthetic block was carried out: the [beta]-azido-glycosides 3a-c, from three subsequent steps. The acetylation reaction of the carbohydrates D-(+)-Glucose, D-(+)-Galactose and L-(+)-Arabinose provided the O-acetyl-glycosides 1a-c, which were used in the next step with a solution 33 % HBr/AcOH to obtain [alfa]-bromo-glycosides 2a-c. Finally, we continued with the azidation reaction that formed the [beta]-azido-glycosides with moderate yields of 49% (3a) and 55% (3b) after crystallization in dichloromethane/ethanol (1:1); and 55% (3b) and 45% (3c) after purification by column chromatography (hexane/ethyl acetate, 8:2). The second synthetic block was prepared from the reaction of the nucleotidic bases, uracil and fluorouracil, with the propargyl bromide which provided the N1-,N3-bis-alkylated pyrimidine bases 4a-b with yields of 88% and 96%. Thus, the triazole nuclei were obtained through the copper-catalyzed 1,3-dipolar cycloaddition reaction between [beta]-azido-glycosides 3a-c and N1-,N3-bis-alkylated pyrimidine bases 4a-c. The disubstituted 1,2,3-triazole derivatives 5a-i were synthesized in excellent yields between 82-99%, and with the reaction time reduced to 1 hour compared to the literature, using 20 mol% of Cu(I) and 20 mol% Et3N.