Synthesis of C-Nucleoside Analogues of 2',3'-Dideoxycytidine, 3'-Azido-2',3'-dideoxyuridine (CS-87), and 2',3'-Dideoxy-2',3'-didehydrocytidine

Article abstract of DOI:10.1021/jo00247a022

C-Nucleoside analogues of 2',3'-dideoxycytidine, 3'-azido-2',3'-dideoxyuridine (CS-87), and 2',3'-dideoxy-2',3'-didehydrocytidine were synthesized from pseudouridine.The C-nucleoside analogue of 2',3'-dideoxycytidine 4a was prepared by stepwise deoxygenation of 1,3-dimethylpseudouridine (11a) followed by the ring transformation of the uracil to the isocytosine ring.Reduction of the dimethylxanthate 11c to 2',3'-unsaturated derivative 13 followed by the ring transformation reaction afforded the C-nucleoside analogue of 2',3'-dideoxy-2',3'-didehydrocytidine (5).Finally, the C-nucleoside analogue of 3'-azido-2',3'-dideoxyuridine (CS-87, 6) was prepared from 2'-deoxypseudouridine (22a) as the intermediate, in which the 3'-OH was oxidized to a 3'-keto moiety followed by reduction to yield 25a.Mesylation and displacement of the mesyl group of 25a by the azide moiety followed by deblocking of the silyl protecting group yielded the desired compound 6