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Posted on March 29, 2017
Date - March 29, 2017
MS Thesis – 602
Title: “Formation of Bicycles and Spirocycles via Desymmetrization.”
Biologically active naturally produced and synthetic compounds often feature chiral centers and heteroatoms. The inclusion of these heteroatoms in cyclic motifs such as lactones and lactams with specific stereochemistry is common. While naturally produced compounds can be isolated, often the small quantities that can be collected are not sufficient for extensive testing or commercial production. This yield issue can be overcome by total synthesis of the natural compound. Additionally, the total synthesis of complex bioactive compounds allows for the derivatization of the structure, which can be used to improve efficacy or better understand the mechanism of action. To effectively produce natural products efficient methodologies for enantioselectively synthesizing complex motifs, such as spirocycles and bicycles, are needed.
The research described in this thesis applies the asymmetric synthetic method of desymmetrization to the synthesis of enantioenriched bicyclic and spirocyclic motifs. The symmetric achiral starting materials for both projects are synthesized and then reacted with chiral phosphoric Brønsted acid catalysts to cause enantioselective intramolecular cyclization. While the attempts to form the bicyclic lactone have yet to produce detectable desired product, the work done has shown the ability to synthesize starting materials and given insight into possible productive modifications. The spirocyclic work has expanded the substrate scope started previously in the Petersen group and sets the foundation for a mechanistic pathway study for the spirocyclic formation. The application of the desymmetrization methodology to an increasing number of symmetric substrates explores the wide scope of this reaction mechanism.