Novel Radical Reactions for C-C Bond Formation

C-C 键形成的新颖自由基反应

• 批准号: 10371873
• 负责人: Simon B. Blakey
• 金额: $ 30.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-10 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371873
• 关键词: Acids; Agrochemicals; Alkenes; Anions; Catalysis; Chemicals; Chemistry; Complex; Consumption; Coupling; Cysteine; Development; Disease; Drug Compounding; Electrons; Event; Family; Food production; Goals; Health; Human; Lead; Light; Medicine; Metals; Methods; Modification; Molecular; Mutagenesis; Pathway interactions; Pattern; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Preparation; Process; Reaction; Reagent; Reducing Agents; Research; Temperature; Vinyl Carbamate; base; catalyst; design; functional group; improved; invention; novel; novel strategies; pharmacophore; scaffold; small molecule; tool

Abstract. The construction of valuable complex molecules from readily available chemical precursors is a central goal in synthesis. Bioactive small molecules (including pharmaceuticals and agrochemicals) are especially valuable because they influence human health and global food production. Our overall research goal is to develop new patterns in chemical reactivity that can be utilized in the solution of many diverse and impactful problems. Our lab has developed a family of radical anion-based processes that selectively activate heteroaromatic substrates for selective coupling with a range of different olefin types. Here we seek to extend this mechanistic strategy to the construction of many different valuable compound classes. In Aim 1, we propose a new strategy for the preparation of valuable fluorinated compounds through the cleavage of very strong C–F bonds (in aryl trifluoromethyl groups). We present a number of different ways that activation of these substrates by radical-anion formation could be utilized in bond-forming processes. Aim 2 seeks to utilize aryl and heteroaryl radical anions in the formation of privileged pharmacophores. In Aim 3, we describe a novel strategy for the synthesis of unnatural peptides.

抽象的。 从容易获得的化学前体中构建有价值的复合物分子是一个核心目标 合成。生物活性小分子（包括药物和农业化学）特别有价值 因为它们会影响人类健康和全球粮食生产。我们的总体研究目标是开发新的 化学反应性的模式可用于解决许多潜水员和有影响力的问题。 我们的实验室开发了一个基于自由基阴离子的过程，该过程有选择地激活异芳族 选择性耦合的基板与各种不同的烯烃类型。在这里，我们试图扩展这种机械 构建许多不同有价值的化合物类别的策略。在AIM 1中，我们提出了一个新的 通过非常牢固的C – F键的裂解制备有价值的氟化化合物的策略 （在芳基三氟甲基中）。我们提出了多种不同的方式，使这些底物通过 自由基的形成可用于键合过程。 AIM 2试图利用芳基和异源 在形成特权药理的基础阴离子。在AIM 3中，我们描述了一种新颖的策略 不自然肽的合成。