Fragment-Coupling at Tertiary Carbons: Macrocarpal and Eucalyptin A Derivatives

University Of California-Irvine, Irvine CA

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Abstract

DESCRIPTION (provided by applicant): A vital step in any efficient chemical synthesis of valuable, structurally complex, organic molecules is the step that couples elaborate fragments. When the atoms joined in a fragment-coupling step each posses 3-dimentional character, exhibiting chirality - the union is particularly challenging. The objective of the proposed researc is the development and validation of new methodologies for combining complex fragments of this type. Specifically, the proposed research will investigate the utility of bimolecular reaction of tertiary carbon radicals with carbon-centered electrophiles for fragment coupling and the construction of quaternary-carbon stereocenters. In addition, radical-based methods will be employed to access 1,4-dicarbonyl structural motifs that exhibit inverse polarity. Such chemical transformations are not commonly utilized in organic synthesis, yet hold untapped potential to address formidable challenges faced by the scientific community in constructing complex organic molecules. All of the methods to be developed under this fellowship will employ photoredox catalysis, and, as a result, will be particularly attractive for their low environmental impact and use of sustainable energy source, visible light. The developed methods will be utilized to generate a library of structural analogs of macrocarpal A, a natural product that exhibits anticancer activity. Antitumor studies will be performed in collaboration with Dr. David Horne to establish advanced structure-activity relationships. The developed body of knowledge should prove valuable in the discovery, and potentially production, of fine chemicals in the pharmaceutical, biotechnology, agricultural, and related industries.