Phosphorylation of 5'-Deoxy-5-fluorouridine with Inorganic Phosphorylating Agents

The phosphorylation of 5′-deoxy-5-fluorouridine (doxifluridine, 5′-DFUR) has been achieved using inorganic cyclo-triphosphate (P3m, Na3P3O9) and monoimido-cyclo-triphosphate (MCTP, Na3P3O8NH) in aqueous solution. In the reaction of 5′-DFUR with P3m, 2′-monophospho-5′-DFUR and 3′-monophospho-5′-DFUR were synthesized with a total yield of more than 95%. In the reaction of 5′-DFUR with MCTP, 2′-diphosphoramidophosphono-5′-DFUR and 3′-diphosphoramidophosphono-5′-DFUR were synthesized with a total yield of more than 40%. The phosphorylated products with P3m and MCTP were stable in neutral and alkaline solutions.