Studies on the Chemistry of Pyrimidine Derivatives with Dimethyldioxirane: Synthesis, Cytotoxic Effect and Antiviral Activity of New 5,6-Oxiranyl-5,6-dihydro and 5-Hydroxy-5,6-dihydro-6- substituted Uracil Derivatives and Pyrimidine Nucleosides

The oxidation of uracil derivatives and pyrimidine nucleosides performed in CH2Cl2 with dimethyldioxirane afforded new 5,6-oxiranyl-5,6-dihydro and cis-/trans-5,6-dihydroxy-5,6-dihydro-derivatives. When the oxidations were performed in the presence of methanol as nucleophile cis- and trans-5-hydroxy-6-methoxy-5,6-dihydro derivatives were obtained in acceptable yields. Cis- and trans-1,3-dimethyl-5-hydroxy-6-alkylamino-5,6-dihy uracils were obtained by nucleophilic ring opening of the 1,3-dimethyl-5,6-oxiranyl-5,6-dihydro uracil in the purified form. Interestingly some of the new title products revealed low cytotoxicity and selective antiviral activity against DNA and RNA Viruses. In particular, compound 17b shows a strong and selective inhibition of the Sendai virus with lower effect on Herpes Simplex-1 virus. Compound 17b is also able to slightly inhibit HIV-1 virus at high concentrations, but in this case a cytotoxic effect was observed.