Carbocyclic phosphonate-based nucleotide analogs related to PMEA .1. Racemic trans-configured derivatives

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 tosyloxy-methanephosphonate. 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.