Synthesis and testing of novel dioxolane-based compounds with antiplasmodial activity

AEI 77

Derek C. Martyn, dmartyn@broad.mit.edu1, Meaghan J. Beattie1, Armando Ramirez, apramire@uci.edu2, Joseph Cortese1, Vishal Patel1, Keith A. Woerpel2, and Jon Clardy, jon_clardy@hms.harvard.edu3. (1) Infectious Diseases Initiative, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, (2) Department of Chemistry, University of California, Irvine, Irvine, CA 92717-2025, (3) Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115
Endoperoxide-based compounds play an important role in the treatment of malaria. Artemisinin, a natural product isolated from the bark of the wormwood tree in China, is widely adopted as part of a combination therapy in the treatment of uncomplicated malaria. Semisynthetic derivatives of artemisinin are also in clinical use. However, the worldwide supply of artemisinin is limited, and the development of resistance to this compound has been demonstrated in the laboratory. We have an interest in developing low-cost, short synthetic routes towards endoperoxides that may still prove effective after artemisinin resistance arises in the clinic. To this end, we are utilizing an SnCl4-mediated annulation strategy to form a 1,2-dioxolane core that would act as the reactive functionality to induce parasite death. Preliminary synthetic and assay results have revealed the ease by which these compounds can be synthesized, and their activity in a live/dead Plasmodium falciparum assay.
 

Academic Employment Initiative
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Academic Employment Initiative

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007