Synthesis and antiviral activity evaluation of novel 2-phenyl-4-(d-arabino-4′-cycloaminobutyl)triazoles: acyclonucleosides containing unnatural bases

Abstract

Five 2-phenyl-4-(d-arabino-4′-cycloamino-3′-hydroxy-O-1′,2′-isopropylidene-butyl)-2H-1,2,3-triazoles, acyclonucleosides containing unnatural bases have been synthesised by opening of the epoxide ring of 2-phenyl-4-(d-arabino-3′,4′-epoxy-O-1′,2′-isopropylidenebutyl)-2H-1,2,3-triazole with the corresponding cyclic amines in 70–85% yields. The starting arabino-epoxytriazole was prepared in five steps starting from d-glucose in an overall yield of 15%. All the five triazolylacyclonucleosides were unambiguously identified on the basis of their spectral data. The structure of one of the intermediates, that is 2-phenyl-4-(d-arabino-1′,2′,3′,4′-tetrahydroxybutyl)-2H-1,2,3-triazole was confirmed by its X-ray crystallographic studies. These acyclonucleosides were subjected to antiviral activity evaluation in CEM-SS cell-based anti HIV assay with the lymphocytropic virus strains HIV-1IIIB and HIV-1RF.