Total Synthesis of Plocamium Polyhalogenated Monoterpenes, Analogues, and Biologi

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DESCRIPTION (provided by applicant): Plocamium polyhalogenated monoterpenes are metabolites first isolated from the red algae Plocamium cartilagineum, featuring several units of unsaturation, as well as multiple halogens, including two contiguous stereogenic chlorine-bearing carbons. These molecules possess a wide range of biological activity, but most notably show cytotoxicity against a range of solid-tumor cancer cell lines. This promising activity has caught the attention of William Gerwick (Scripps Institution of Oceanography) and Dr. Fred Valeriote (Henry Ford Medical Center). The testing of several members of the Plocamium polyhalogenated monoterpene family suggests only moderate cytotoxicity levels, initial results indicate that these compounds are selective for solid tumors, while remaining nontoxic to healthy cells. However, due to the low abundance from natural sources, these compounds were only isolated in small quantities, and in vivo studies could not be conducted. The Vanderwal group at the University of California Irvine aims to develop the first synthesis of members of the Plocamium polyhalogenated monoterpenes, The proposed synthesis is concise and modular, allowing for multiple members of the class to be synthesized, as well as a host of unnatural analogues, with only minor modifications to the procedure. Initial results on the synthesis of simplified model systems are promising, and once completed, the Plocamium polyhalogenated monoterpene natural products will be synthesized. Through collaboration with Gerwick and Dr. Valeriote, the synthesized compounds will be tested for biological activity, and in the case of known bioactive members, continue in vivo studies.