Discovery of a new template for anticancer agents: 2′-deoxy-2′- fluoro-4′-selenoarabinofuranosyl-cytosine (2′-F-4′-seleno-ara- C)

The first synthesis of 2′-deoxy-2′-fluoro-4′- selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4′-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2′-F-4′-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was more potent than ara-C (1).