Protecting groups in nucleoside syntheses. IV. 5′-Halogeno-5′-deoxy-2′, 3′-cyclic sulphite isomers in the preparation of 5′-halogeno-5′-deoxy nucleosides

Abstract

Two isomeric 5′-halogeno-2′,3′-sulphites, epimeric at sulphur atom, are formed from ribonucleosides with thionyl chloride-hexamethylphosphoric triamide reagent. The formation of 5′-chloro-2′,3′-sulphites with cytidine (95%) and/or adenosine (94%) in acetonitrile supports a new proposal of the reaction mechanism. 5′-Choro-2′3′-sulphinylcytidine is converted to 5′-chloro- and 5′-deoxycytidine and/or to the 2,2′-anhydro nucleoside and to the 5′-chloro- and 5′-deoxyarabinosylcytosine. 5-Chloro and 5′-deoxy derivatives of adenosine are described. The activity of the analogues of 5-fluorouracil towards the inhibition of RNA and DNA synthesis in cultured L1210 leukemia cells is compared.