CARBOCYCLIC PHOSPHONATE-BASED NUCLEOTIDE ANALOGS RELATED TO PMEA .2. RACEMIC CIS-CONFIGURED DERIVATIVES

Racemic N-(cis-2-phosphonmethoxycycloalkyl) derivatives of heterocycli c bases, a novel type of nucleotide analogs related io 9-(2-phosphonom ethoxyethyl)adenine (PMEA), are reported. The synthesis of adenine- (6 a, 6b), uracil- (6c) and cytosine- (6d) containing carbocyclic phospho nates 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 processed nucleobases with trans-2-benzyl oxycycloalkanols, whereas pyrimidine-containing nucleoside analogs 5g- 5k were obtained by configurational inversion at C-2' of the correspon ding 1-(trans-2-hydroxycycloalkyl)pyrimidines via ring opening of thei r 2,2'-anhydro derivatives.