Synthesis and RT inhibitory activity evaluation of new pyrimidine-based seco-nucleosides

Eleven new 3',4'-seco acyclic nucleosides (4-14) were prepared by nucleophilic substitution of protected pyrimidine bases on ethyl 3,3-diethoxypropanoate (3). Structures were characterized spectroscopically and a brief analysis of their conformation in solution was performed by the vicinal coupling constants (3)JH2'aH3' and (3)JH2'bH3'. In solid state, compound 6 forms a homodimer linked by hydrogen bonding. In preliminary tests all compounds show low toxicity and gentle activity against HIV-1 RT in vitro.