CHEMOENZYMATIC SYNTHESIS OF 3′-DEOXY-3′-(4-SUBSTITUTED-TRIAZOL-1-YL)-5-METHYLURIDINE

An efficient protocol has been developed for the synthesis of a small library of 3-deoxy-3-(4-substituted-triazol-1-yl)-5-methyluridine using Cu(I)-catalyzed Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition reaction of 3-azido-3-deoxy-5-methyluridine with different alkynes under optimized condition in an overall yields of 76%-92%. Here, the azido precursor compound, i.e., 3-azido-3-deoxy-5-methyluridine was chemoenzymatically synthesized from D-xylose in good yield. Some of the alkynes used in cycloaddition reaction were synthesized by the reaction of hydroxycoumarins or naphthols with propargyl bromide in acetone using K(2)CO(3)in excellent yields. All synthesized compounds were unambiguously identified on the basis of their spectral (IR, H-1-, C-13 NMR spectra, and high-resolution mass spectra) data analysis.