Replacement of the phosphodiester linkage in oligonucleotides by heterocycles: synthesis of thymidine dinucleotide analogs with triazole-modified backbones

Novel backbone-modified dinucleotide analogs of types V and VI have been synthesized, where the natural phosphodiester linkage of a T-T dinucleotide has been replaced by a triazole heterocycle. The key step of the synthesis is the regioselective, thermal cycloaddition of a 2-oxoalkylidene triphenylphosphorane with an azide derivative to generate the triazole ring.