Simple transformation of thymine 1-[3-hydroxy-2-(phosphono-methoxy)propyl] derivatives to their 1-[3-fluoro-2(phosphonomethoxy)propyl] counterparts

A novel method of transformation of HOCH2 group to FCH2 was successfully applied to the preparation of fluorine-containing pyrimidine acyclic nucleoside phosphonates ( FPMP compounds) such as (S)- and (R)- 1-[3-fluoro-2-(phosphonomethoxy) propyl] thymine (7a, 7b) (FPMPT). The key displacement of hydroxy group with fluorine in 1-{2-[(diisopropoxyphosphoryl)methoxy]- 3-hydroxypropyl}-4-methoxy-5-methylpyrimidin-2(1H)- one (5a, 5b) was performed using perfluorobutane-1-sulfonyl fluoride in the presence of DBU. Novel pyrimidine acyclic nucleoside phosphonates were investigated as inhibitors of thymidine phosphorylase.