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Synthesis of spiro-1,2-dioxolanes and their activity against Plasmodium falciparum.
|Publication Type||Journal Article|
|Authors||Martyn, DC, Ramirez AP, Beattie MJ, Cortese JF, Patel V., Rush MA, Woerpel KA, and Clardy J.|
|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 SnCl(4)-mediated annulation of a bis-silylperoxide and an alkene. The first set of eight analogs gave EC(50) 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 (EC(50) approximately 5 nM).|
|Year of Publication||2008|
|Journal||Bioorganic & medicinal chemistry letters|
|Date Published (YYYY/MM/DD)||2008/12/15|