Asymmetric Synthesis of Exiguaquinol and Analogs for Biological Testing

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DESCRIPTION (provided by applicant): Exiguaquinol was first isolated from the marine sponge, Neopetrosia exigua, and contains five fused rings, four contiguous stereogenic centers, an aryl sulfate and an alkyl sulfonate.1 Discovered in a screen for inhibitors of Helicobacter pylori MurI, it is the first natural product reported to inhibit this enzyme. H. pylori is a pathognic bacterium known to cause prolonged gastritis and sharply increased risks for gastric cancer and the MurI enzyme is critical to cell wall biosynthesis.1,2 Therefore, we believe exiguaquinol is an excellent lead target for bacterial treatment of H. pylori infection without disruption of beneficil gut bacteria. However, due to the scarcity of material isolated from remote natural sources, limited studies have been performed on exiguaquinol and synthesis is the best way to access larger quantities of exiguaquinol for testing. Through my research in the Vanderwal lab at University of California, Irvine, we have completed a synthesis of the core of the natural product and aim to complete the first total synthesis of exiguaquinol. Our proposed synthesis (see Research Strategy) is direct, asymmetric and modular and allows for the synthesis of unnatural analogs with strategic modifications. Once completed, exiguaquinol and its synthetic analogs will be screened for MurI inhibition and also analyzed for cytotoxicity and anti- cancer activity.