Thursday, November 21, 2024
11/21/2024
DESCRIPTION (provided by applicant): Fused-bicyclic alkaloids show promise as therapeutic agents to combat a number of human illnesses; including cancer, migraine headaches, hypertension, thrombosis, and malaria. As a consequence, the development of new pathways to access these important compounds through chemical synthesis has been a top priority of researchers. Nonetheless, existing methods generally require many chemical steps, some of which involve harsh reaction conditions, to generate the final products. Often times the products exist as complex mixtures of isomers that can be difficult to separate. Moreover, stereospecific and stereo divergent pathways to these alkaloids remain underexplored. To overcome these limitations, the proposed research will focus on the development of new and efficient synthetic pathways to fused-bicyclic alkaloids from oxazolium salts. Oxazolium salts are readily available, yet under-utilized building blocks in chemical synthesis. They generally react rapidly under mild reaction conditions and afford largely one isomeric product. Building on preliminary results, the specific aims of the proposed research will focus on the construction of two classes of bicyclic alkaloids, specifically octahydroindoles (OHIs) and decahydroquinolines (DHQs). Both of these classes of alkaloids are of high importance for their wide-ranging biological activities. These studies will lead to a well-defined method for the synthesis of diverse fused-bicyclic alkaloids with predictable stereochemical results. Such methods will surmount current barriers to further development of bicyclic alkaloids as successful pharmaceuticals and chemical tools for biology. The proposed research will also have a tremendous positive impact on the research environment at Salisbury University through the engagement of undergraduate students in research projects at the forefront of alkaloid synthesis, likely propelling them to future careers n the chemical and biomedical sciences.
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