Studies have shown that chemical structures with sp3 chiral carbons allow for more complex molecules that are biologically active, more soluble, and more selective. However, the most commonly used chemistry synthetic tools in the pharmaceutical industry create flat aromatic and sp2 carbon structures. Therefore, the development of better synthetic tools to generate drugs with sp3 chiral centers would benefit the pharmaceutical industry in their efforts to make more successful drugs, with fewer side effects and better bioavailability. Research in our lab has been focused on demonstrating the Birch-Heck sequence, a new synthetic tool, to generate sp3 chiral centers in tricyclic structures, and this project extends these methods to the synthesis of phenanthridinone analogs with sp3 stereocenters. Since the phenanthridinone core has been found to be active in 3,200 different assays, it has important and broad biological activity. Incorporating an sp3 quaternary carbon in carbazole would potentially increase selectivity, while maintaining its bioactivity for therapeutic purposes. The new synthetic chemistry tool involves a short sequence of reactions to rapidly generate fused tricyclic ring systems with a chiral quaternary or tertiary center. The process involves desymmetrizing cyclohexadiene structures generated in the versatile Birch reduction-alkylation reaction. The use of palladium catalysts with chiral ligands in a desymmetrizing Mizoroki-Heck reaction will afford enantioselective control in the key step. The versatility of the Mizoroki-Heck reaction will allow the creation of a broad range of structures, including medium-size and heterocyclic rings. In the process, the substrate scope of the enantioselective intramolecular Mirzoroki-Heck reaction will be expanded.

Development of complex chiral phenanthridinone analogs via the enantioselective Birch-Heck reaction sequence

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.