Synthesis and Potent Antimalarial Activity of Kalihinol B

Mary Elisabeth Daub^†, Jacques Prudhomme^‡, Karine Le Roch^‡, and Christopher D. Vanderwal^*^†

^† Department of Chemistry, University of California, Irvine, 1102 Natural Sciences II, Irvine, California 92697-2025, United States

^‡ Department of Cell Biology and Neuroscience, University of California, Riverside, 900 University Avenue, Riverside, California 92521, United States

J. Am. Chem. Soc., 2015, 137 (15), pp 4912–4915

DOI: 10.1021/jacs.5b01152

Publication Date (Web): March 27, 2015

*cdv@uci.edu

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Abstract

Of the 50+ kalihinane diterpenoids reported to date, only five had been tested for antimalarial activity, in spite of the fact that kalihinol A is the most potent among the members of the larger family of antimalarial isocyanoterpenes. We have validated a strategy designed to access many of the kalihinanes with a 12-step enantioselective synthesis of kalihinol B, the tetrahydrofuran isomer of kalihinol A (a tetrahydropyran). Kalihinol B shows similarly high potency against chloroquine-resistant Plasmodium falciparum.

Supporting Information

Experimental procedures and characterization data for all new compounds, X-ray crystallographic structure and information for 21 (CIF), and complete ref 8b. This material is available free of charge via the Internet at http://pubs.acs.org.

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