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

Raffaele Saladino, Roberta Bernini, Claudia Crestini, Enrico Mincione, Alberto Bergamini, Stefano Marini, Anna Teresa Palamara

Research output: Contribution to journalArticle

Abstract

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-dihvdroxv-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-dihydro 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.

Original languageEnglish
Pages (from-to)7561-7578
Number of pages18
JournalTetrahedron
Volume51
Issue number27
DOIs
Publication statusPublished - Jul 3 1995

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Pyrimidine Nucleosides
Uracil
Viruses
Antiviral Agents
Derivatives
Sendai virus
DNA Viruses
RNA Viruses
Human Herpesvirus 1
Oxidation
Nucleophiles
Methanol
HIV-1
Cytotoxicity
RNA
pyrimidine
dimethyldioxirane
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

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. / Saladino, Raffaele; Bernini, Roberta; Crestini, Claudia; Mincione, Enrico; Bergamini, Alberto; Marini, Stefano; Teresa Palamara, Anna.

In: Tetrahedron, Vol. 51, No. 27, 03.07.1995, p. 7561-7578.

Research output: Contribution to journalArticle

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