Collect. Czech. Chem. Commun. 2005, 70, 2066-2074

Synthesis of N4-Substituted Derivatives of 1-[2-(Phosphonomethoxy)ethyl]cytosine and Its Diisopropyl Ester as a Model Reaction for the Synthesis of N4-Substituted Derivatives of Cidofovir

Šárka Chalupová*, Antonín Holý and Milena Masojídková

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


We have studied the reaction of 1-[2-(phosphonomethoxy)ethyl]cytosine (1) and its diisopropyl ester (2) with triethylammonium hydrogensulfite in 60% aqueous methanol. In the presence of some primary or secondary amine salts, at 25-70 °C, this reaction affords transaminated derivatives 4a-4e and 5a, 5b as main products accompanied by uracil compounds. However, with certain amines the reaction failed.

Keywords: Cytosine modification; Antivirals; Cidofovir; HPMPC; Acyclic nucleoside phosphonates; Nucleotides; Pyrimidines; Transamination; Amines.

References: 10 live references.