Synthesis of 3′-β-carbamoylmethylcytidine (CAMC) and its derivatives as potential antitumor agents

Abstract

3′-β-Carbamoylmethylcytidine (CAMC) and its derivatives were synthesized using an intramolecular Reformatsky-type reaction promoted by SmI₂ as the key step. In vitro tumor cell growth inhibitory activity was evaluated and CAMC was found to exhibit potent cytotoxicity against various human tumor cell lines. From a structure–activity relationship study it was postulated that the cytotoxic mechanism of action of CAMC did not require phosphorylation at the 5′-hydroxyl group. This study provides a novel strategy for the development of a new type of antitumor nucleoside.