Synthetic Studies on Rare and Novel Marine Alkaloids

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ABSTRACTWith this award, the Chemical Synthesis Program of the Chemistry Division is funding Professor Gary Sulikowski of the Department of Chemistry at Vanderbilt University to develop synthetic routes to structurally novel and rare marine alkaloids isolated from marine sponges. This work provides efficient methods to access marine natural products for biomedical study. The chemistry developed during the course of these studies has a broad relevance in areas ranging from the pharmaceutical, chemical, and biotechnology industries to basic biological and chemical research endeavors. The marine natural products of interest possess unique molecular structures with minimal information on their biological properties and potential as therapeutic leads. Studies include the synthesis of upenamide, halicyclamines, xestocyclamine and haliclonin A marine alkaloids. The chemical synthesis of these natural products enables deeper investigation into their biological properties and a foundation for use as therapeutic agents for the treatment of cancer and microbial infections. In addition, the project provides excellent training of graduate and undergraduate students for entry into the pharmaceutical and chemical industry.In each proposed chemical synthesis, new transformations are incorporated into multi-step synthetic schemes enabling the assembly of not only the marine alkaloids of interest but advance nitrogen heterocycle synthesis broadly. The use of bromomaleic anhydride as a dienophile in stereoselective Diels-Alder reactions is featured in each proposed total synthesis. The products of the key cycloaddition reaction are advanced to complex polycyclic structures by employing reactions that take advantage of key stereochemistry and functionality emerging from the initial Diels-Alder reaction.