[摘要]：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 similar to 5 nM). (C) 2008 Elsevier Ltd. All rights reserved.
