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

三级碳的片段偶联：大果醛和桉树素 A 衍生物

• 批准号: 8834139
• 负责人: Yuriy Slutskyy
• 金额: $ 3.7万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8834139
• 关键词: Address; Agriculture; Alcohols; Alkenes; Award; Biological; Biological Factors; Biotechnology; Carbon; Catalysis; Cessation of life; Chemicals; Collaborations; Communities; Complex; Coupled; Couples; Coupling; Development; Electrons; Energy-Generating Resources; Environmental Impact; Eucalyptus; Exhibits; Face; Family; Felis catus; Fellowship; Industry; Knowledge; Libraries; Link; Malignant Neoplasms; Methodology; Methods; Organic Synthesis; Oxalates; Pharmacologic Substance; Phloroglucinol; Plague; Plants; Positioning Attribute; Preparation; Process; Production; Reaction; Reagent; Reducing Agents; Reporting; Research; Research Institute; Structure-Activity Relationship; Terpenes; Validation; Visible Radiation; analog; anticancer activity; base; chemical synthesis; drug candidate; drug discovery; method development; oxoamide; professor; public health relevance; research study; small molecule libraries; success

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.

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，一个至关重要的步骤是耦合精细片段的步骤。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 - 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此类复杂片段的新方法。具体来说，拟议的研究将研究叔碳自由基与碳中心亲电子试剂的双分子反应在片段偶联和季碳立构中心构建中的效用。此外，将采用基于自由基的方法来获取表现出反极性的 1,4-二羰基结构基序。这种化学转化在有机合成中并不常用，但在解决科学界在构建复杂有机分子方面面临的巨大挑战方面具有尚未开发的潜力。该奖学金下开发的所有方法都将采用光氧化还原催化，因此，因其低环境影响而特别有吸引力 可持续能源、可见光的影响和使用。开发的方法将用于生成 Macrocarpal A 的结构类似物库，macrocarpal A 是一种具有抗癌活性的天然产物。将与 David Horne 博士合作进行抗肿瘤研究，以建立先进的结构-活性关系。成熟的知识体系在制药、生物技术、农业和相关行业的精细化学品的发现和潜在生产中具有价值。