Efficient incorporation of 1-(2-deoxy-beta-D-ribofuranosyl)-2-oxo-imidazole-4-carboxamide into DNA via a suitable convertible phosphoramidite derivative

Abstract : The synthetic scheme of 1-(2-deoxy-beta-D-ribofuranosyl)-2-oxo-imidazole-4-carboxamide (3) is based on the ring contraction of pyrimidine (5-BrdU) into imidazolin-2-one. The rearrangement leads to the unexpected Mixture of the deoxynucleoside 4 beta and its alpha anomer. The mechanism of the anomerisation under basic conditions is proposed. Further conversion of 4-carboxylic acid into amide affords the title compound 3. The conversion of 4-carboxylic acid into ethyl ester is preferred for the preparation of the phosphoramidite derivative 11 suitable for chemical incorporation of the modified nucleobase into DNA. Thermal denaturation studies show that 2-oxoY within the sequence used pairs more favorably with the purines than the pyrimidines.