Collect. Czech. Chem. Commun. 1996, 61, 778-790

Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA II. Racemic cis-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 N-(cis-2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of adenine- (6a, 6b), uracil- (6c) and cytosine- (6d) containing carbocyclic phosphonates is based on the reaction of cis-2-hydroxycycloalkyl derivatives of protected nucleobases with diisopropyl tosyloxymethanephosphonate. The starting purine-containing nucleoside analogs 5a-5f were prepared by the Mitsunobu reaction of protected nucleobases with trans-2-benzyloxycycloalkanols, whereas pyrimidine-containing nucleoside analogs 5g-5k were obtained by configurational inversion at C-2' of the corresponding 1-(trans-2-hydroxycycloalkyl)pyrimidines via ring opening of their 2,2'-anhydro derivatives.

Keywords: Carbocyclic analogs; Antivirals; Nucleoside phosphonates.