Synthesis of spiro-1,2-dioxolanes and their activity against Plasmodium falciparum

Derek C. Martyn, Armando P. Ramirez, Meaghan J. Beattie, Joseph F. Cortese, Vishal Patel, Margaret A. Rush, K. A. Woerpel, Jon Clardy

Research output: Contribution to journalArticlepeer-review

Abstract

Artemisinin-derived compounds play an integral role in current malaria chemotherapy. Given the virtual certainty of emerging resistance, we have investigated spiro-1,2-dioxolanes as an alternative scaffold. The endoperoxide functionality was generated by the SnCl4-mediated annulation of a bis-silylperoxide and an alkene. The first set of eight analogs gave EC50 values of 50-150 nM against Plasmodium falciparum 3D7 and Dd2 strains, except for the carboxylic acid analog. A second series, synthesized by coupling a spiro-1,2-dioxolane carboxylic acid to four separate amines, afforded the most potent compound (EC50 ∼5 nM).

Original languageEnglish (US)
Pages (from-to)6521-6524
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number24
DOIs
StatePublished - Dec 15 2008

Keywords

  • Dioxolane
  • Endoperoxide
  • Malaria
  • Plasmodium

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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