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

描述（由申请人提供）：在任何有价值的、结构复杂的有机分子的有效化学合成中，将精细的片段偶联是至关重要的一步。当原子在片段耦合步骤中结合时，每个原子都具有三维特征，表现出手性-结合特别具有挑战性。拟议研究的目标是开发和验证结合这种类型的复杂片段的新方法。具体而言，本研究将探讨叔碳自由基与碳中心亲电试剂的双分子反应在片段偶联和季碳立体中心构建中的应用。此外，基于自由基的方法将被用于获取具有反极性的1,4-二羰基结构基序。这种化学转化在有机合成中并不常用，但在解决科学界在构建复杂有机分子时面临的巨大挑战方面具有未开发的潜力。所有在这项奖学金下开发的方法都将采用光氧化还原催化，因此，它们的低环境将特别有吸引力

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.