Session: Undergraduate Research Posters: Organic Chemistry:

Our research worked to develop effective techniques for chiral all-carbon quaternary center synthesis using the Birch-Heck sequence. Studies have shown that many drug candidates fail in clinical trials because they have too few sp3 carbons and chiral centers. Flat structures like phenanthridinone have wide, but non-selective bioactivity because they can interact with many different proteins. Creating a phenanthridone analog with a chiral quaternary center may make for a more selective and effective compound as a medication. The process started with the Birch reductive alkylation reaction using cheap, readily available materials and produced a symmetrical molecule with a newly created all-carbon quaternary center. The Birch reaction product was coupled with haloanilines or aminophenols to afford the substrates for the Heck reaction. Palladium or nickel catalysts were used with chiral ligands in a desymmetrizing Heck reaction to create chiral quaternary centers. The Heck reaction afforded a tri-cyclic molecule analogous to phenanthridinone, but with a chiral quaternary center. The products will be tested for bioactivity against poly (ADP-ribose) polymerase (PARP), an important anti-cancer target. If successful, our work will improve access to chiral quaternary carbon center containing compounds for pharmaceutical use.

William Malachowski

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