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，关键的一步是将精细片段偶联。当原子在片段耦合步骤中连接时，每个原子都具有三维特征，表现出手性--这种结合特别具有挑战性。拟议研究的目标是开发和验证用于组合这类复杂片段的新方法。具体地说，拟议的研究将探索叔碳自由基与碳心亲电分子的双分子反应在片段偶联和构建四元碳立体中心方面的应用。此外，基于自由基的方法将被用来获得表现出反极性的1，4-二羰基结构基序。这种化学转化在有机合成中并不常见，但具有尚未开发的潜力，可以解决科学界在构建复杂有机分子方面面临的严峻挑战。根据这一合作关系开发的所有方法都将采用光氧化还原催化，因此，由于它们对环境的影响较小，因此将特别有吸引力。 可持续能源、可见光的影响和使用。开发的方法将被用来生成一个大腕A的结构类似物库，大腕A是一种具有抗癌活性的天然产物。将与大卫·霍恩博士合作进行抗肿瘤研究，以建立高级结构-活性关系。已开发的知识体系在制药、生物技术、农业和相关行业的精细化学品的发现和潜在的生产中应该被证明是有价值的。

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.