A conformationally locked tricyclic nucleoside. Synthesis, crystal structure and incorporation into oligonucleotides

A tricyclic nucleoside is synthesised from a bicyclic nucleoside precursor by applying a stereoselective dihydroxylation, a regioselective tosylation and an intramolecular ether formation. This tricyclic nucleoside is constructed as a conformationally locked thymidine analogue and has been analysed by X-ray crystallography. Thus, the furanose ring of this nucleoside adopts a perfect S-type conformation and the torsion angle γ, describing the C4′–C5′ bond is restricted in the +ac range. The tricyclic nucleoside is incorporated into two nonameric oligonucleotide sequences displaying strongly decreased affinity towards complementary DNA and RNA when compared to the corresponding unmodified oligodeoxynucleotide sequences.