Scientific Publications

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

Publication TypeJournal Article
AuthorsMartyn, DC, Ramirez AP, Beattie MJ, Cortese JF, Patel V., Rush MA, Woerpel KA, and Clardy J.
AbstractArtemisinin-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 Publication2008
JournalBioorganic & medicinal chemistry letters
Date Published (YYYY/MM/DD)2008/12/15
ISSN Number0960-894X