Collect. Czech. Chem. Commun. 2005, 70, 1465-1481

Simple Transformation of Thymine 1-[3-Hydroxy-2-(phosphonomethoxy)propyl] Derivatives to Their 1-[3-Fluoro-2-(phosphonomethoxy)propyl] Counterparts

Karel Pomeisl*, Radek Pohl, Antonín Holý and Ivan Votruba

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, CZ-166 10, Prague 6, Czech Republic


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.

Keywords: Acyclic nucleoside phosphonates; Acyclic nucleotide analogues; Thymidine phosphorylase; Deoxyfluorinations; Thymine; Pyrimidines; Antivirals.

References: 29 live references.