CARBOCYCLIC PHOSPHONATE-BASED NUCLEOTIDE ANALOGS RELATED TO PMEA .1. RACEMIC TRANS-CONFIGURED DERIVATIVES

Racemic trans-N-(2-phosphonomethoxycycloalkyl) derivatives of heterocy clic bases, a novel type of nucleotide analogs related to 9-(2-phospho nomethoxyethyl)adenine (PMEA), are reported. The synthesis of fully pr otected adenine- (5), hypoxanthine- (7), guanine- (11), thymine- (13), uracil- (16) and cytosine-containing (18) carbocyclic nucleotide anal ogs is based on the reaction of trans-2-hydroxycycloalkyl derivatives of N-protected nucleobases (2, 10, 12, 14, 17) with diisopropyl tosylo xy-methanephosphonate. Deprotection of these compounds afforded the ti tle nucleotide analogs. The starting ''nucleoside'' derivatives have b een prepared via nucleophilic oxirane ring opening of cycloalkene oxid es with various protected or free nucleobases.