Article ID Journal Published Year Pages File Type
1374800 Bioorganic & Medicinal Chemistry Letters 2008 4 Pages PDF
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).

Graphical abstractA SnCl4-mediated annulation was utilized to form a series of 1,2-dioxolanes, which were tested for activity against multiple strains of Plasmodium falciparum.Figure optionsDownload full-size imageDownload as PowerPoint slide

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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