Collect. Czech. Chem. Commun. 1996, 61, 313-332

Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA. I. Racemic trans-Configured Derivatives

Radek Liboska, Milena Masojídková and Ivan Rosenberg

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


Racemic trans-N-(2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of fully protected adenine- (5), hypoxanthine- (7), guanine- (11), thymine- (13), uracil- (16) and cytosine-containing (18) carbocyclic nucleotide analogs is based on the reaction of trans-2-hydroxycycloalkyl derivatives of N-protected nucleobases (2, 10, 12, 14, 17) with diisopropyl tosyloxymethanephosphonate. Deprotection of these compounds afforded the title nucleotide analogs. The starting nucleoside derivatives have been prepared via nucleophilic oxirane ring opening of cycloalkene oxides with various protected or free nucleobases.

Keywords: Nucleotide analogs; Phosphonates; Antivirals.