Design, synthesis and in vitro antimalarial activity of spiroperoxides

Hong Xia Jin, Qi Zhang, Hye Sook Kim, Yusuke Wataya, He Hua Liu, Yikang Wu

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Several spiroperoxy antimalarial compounds were designed and synthesized using the hydrogen peroxide in UHP (urea-H2O2 complex) as the source of the peroxy bond. Incorporation of the H2O2 into the organic molecule framework through ketal exchange reaction in the present cases was greatly facilitated by the potential to form a five- or six-membered cyclic hemiketal due to the presence of a hydroxyl group γ or δ to the ketone carbonyl group. When the electron-withdrawing group in the Michael acceptor was a nitro group, the closure of the peroxy ring occurred readily under the hydroxidation conditions. Presence of a benzene ring fused to the peroxy ring effectively reduced the degrees of freedom in the transition state for the ring-closure step and made the otherwise very difficult seven-membered 1,2-dioxepane rather easy to form through the intramolecular Michael addition.

Original languageEnglish
Pages (from-to)7699-7711
Number of pages13
JournalTetrahedron
Volume62
Issue number33
DOIs
Publication statusPublished - Aug 14 2006

Keywords

  • Antimalarials
  • Cyclizations
  • Hemiketals
  • Peroxides
  • Spiroketals

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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