Abstract The synthesis of cyclo Sal-FdUMP 3 ad as a new prodrug approach for FdU 1 is described. Phosphotriesters 3 release the FdUMP 2 selectively by a controlled, chemically induced tandem reaction in hydrolysis studies. The biological activity (IC50) of cyclo Sal- phosphotriesters 3 was evaluated in FM3A/O cells and FM3A/TK− cells.