Efficient one-pot synthesis of polysubstituted 6-[(1H-1,2,3-triazol-1-yl)methyl]uracils through the “click” protocol

The preparation of several triazolo acyclic nucleosides and triazolo acyclic nucleoside phosphonates is described. The synthetic methodology has been developed as an efficient one-pot Cu(I)-catalyzed azide alkyne Huisgen “click” cycloaddition. A novel Cu(I)-catalyzed decarboxylation reaction of 1-substituted 1H-1,2,3-triazole-4-carboxylic acids at room temperature was observed and used for the preparation of 1-substituted 1H-1,2,3-triazoles. As congeners of TPI (Taiho pharmaceutical inhibitor), the prepared compounds were screened as potential inhibitors of human thymidine phosphorylase, but no inhibitory activity was observed.