Synthesis and Biological Activity of Reversed Pyrimidine Nucleosides

An efficient approach to reversed nucleosides which enables their synthesis in gram quantities is described. N-1'-Pyrimidine reversed nucleosides were prepared by treating of the sodium salt of pyrimidine bases with protected 5-tosyl ribose. Additionally, N-1',N-3'-disubstituted reversed nucleosides were isolated in the condensation reactions with the 5-halogen pyrimidines. Using the Sonogashira coupling of 5'-iodouracil reversed nucleoside with ethynyltrimethyl silane gave 5'-ethynyl derivative which was further transformed into 5'-acetyl reversed nucleoside. Biological activity of deprotected reversed nucleosides was validated on the panel of six human carcinoma cell lines (HeLa, MIAPaCa2, Hep2, NCI-H358, CaCo-2, and HT-29). 5'-Iodouracil derivative displayed moderate growth inhibition activity against human colon carcinoma (CaCo-2) cells.