Synthesis and Application of Isothiocyanato Derivatives of Nucleosides

3'-Deoxy-3'-isothiocyanatothymidine (4), 3',5'-protected 2'-deoxy-2'-isothiocyanatouridine (8), and 2',3'-dideoxy-2'-isothiocyanatouridine (14), respectively, have been prepared from the corresponding 2'- or 3'-amino derivatives. SnCl2, Bu(3)SnH, and dithiothreitol were employed to reduce the 2'- or 3'-azido derivatives to give the aminonucleosides which served as starting materials for the thiocarbonylation. Thiocarbonylation, by either a mixture of carbon disulfide and mercuric oxide or N,N'-thiocarbonyldiimidazole, leads directly to the target molecules in high yields. Furthermore, the direct transformation of azidonucleosides into the corresponding isothiocyanto derivatives via treatment of phosphanimine nucleosides with CS2 is described. Th activity of the isothiocyanate group is used for covalent coupling of different linking molecules or dyes to the carbohydrate moiety of the nucleosides.