Collect. Czech. Chem. Commun. 2006, 71, 543-566

Bifunctional Acyclic Nucleoside Phosphonates. 1. Symmetrical 1,3-Bis[(phosphonomethoxy)propan-2-yl] Derivatives of Purines and Pyrimidines

Silvie Vrbovská*, Antonín Holý, Radek Pohl and Milena Masojídková

Centre for Novel Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


We report here a general method for the synthesis of new symmetrical bis-phosphonates of acyclic nucleosides. 1,3-Bis[(diisopropoxyphosphoryl)methoxy] derivatives of purine and pyrimidine bases were prepared by their reaction with 1,3-bis[(diisopropoxyphosphoryl)-methoxy]propan-2-yl tosylate. Cytosine, uracil and thymine provided regiospecifically N1-isomers. This alkylation regiospecificity applies to several other tosylates of primary and secondary alcohols as well. 6-Chloropurine and 2-amino-6-chloropurine were alkylated in N9 position. Resulting bis-phosphonates were converted to the respective free phosphonic acids and tested for antiviral and cytostatic activity. Despite the fact that no biological activity was found so far, the outcome of this work can serve as a useful tool in synthesis of novel groups of acyclic nucleoside phosphonates (ANPs).

Keywords: Acyclic nucleotide analogues; Acyclic nucleoside phosphonates; ANP; Purines; Pyrimidines; Phosphonomethyl ethers; Biphosphonates; Antivirals.

References: 13 live references.