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 perform ed in CH2Cl2 with dimethyldioxirane afforded new 5,6-oxiranyl-5,6-dihy dro and cis-/trans-5,6-dihydroxy-5,6-dihydro-derivatives. When the oxi dations were performed in the presence of methanol as nucleophile cis- and trans-5-hydroxy-6-methoxy-5,6-dihydro derivatives were obtained i n acceptable yields. Cis- and trans-1,3-dimethyl-5-hydroxy-6-alkylamin o-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. Inte restingly some of the new title products revealed low cytotoxicity and selective antiviral activity against DNA and RNA Viruses. In particul ar, compound 17b shows a strong and selective inhibition of the Sendai virus with lower effect on Herpes Simplex-1 virus. Compound 17b is al so able to slightly inhibit HIV-1 virus at high concentrations, but in this case a cytotoxic effect was observed.