|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Martyn, DC, Ramirez, AP, Beattie, MJ, Cortese, JF, Patel, V, Rush, MA, Woerpel, KA, Clardy, J|
|Journal||Bioorganic & medicinal chemistry letters|
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).