Selective Functionalization of Aliphatic Amines

脂肪胺的选择性官能化

• 批准号: 10298573
• 负责人: Tomislav Rovis
• 金额: $ 30.94万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10298573
• 关键词: Alkenes; Alkylation; Amides; Amines; Automobile Driving; Carboxylic Acids; Catalysis; Chemistry; Cobalt; Complex; Copper; Coupling; Distal; Drug Design; FDA approved; Funding; Goals; Health; Hydrogen Bonding; Imines; Metals; Methods; Nickel; Nitrogen; Oxidation-Reduction; Pharmaceutical Preparations; Pharmacologic Substance; Planet Earth; Positioning Attribute; Principal Investigator; Protocols documentation; Reaction; Research; Salts; Site; Sodium Chloride; Structure; Sulfhydryl Compounds; System; Therapeutic Agents; Uncertainty; Work; aryl halide; catalyst; chlorination; dehydrogenation; design; drug discovery; efficacious treatment; functional group; human disease; interest; programs; scaffold; small molecule; success; tertiary amine

Principal Investigator/Program Director (Last, First, Middle): Rovis, Tomislav Selective Functionalization of Aliphatic Amines and Derivatives Aliphatic amines are ubiquitous among pharmaceutical compounds, driving significant research into the synthesis and functionalization of molecules bearing nitrogen atoms. Traditional strategies use functional group handles to synthesize amines. We have been engaged in a research program that uses resident C-H bonds and transforms them directly into the functionality of interest. The central challenge to derivatizing amines, thus, was one of positional selectivity. A number of strategies were advanced in the previous funding period with broad success. In the next funding period, we will expand the repertoire of reactions, the positions of activation and the complementarity to existing methods. We will develop methods to arylate C-H bonds in aliphatic amines, to difunctionalize vicinal C-H bonds in analogy to olefin difunctionalization, again with complete positional selectivity and to use earth abundant metal salts to activate distal C-H bonds of amines. Complementary approaches will be aimed at providing a method to functionalize inaccessible C-H bonds on tertiary amines, common components of many FDA approved drugs. These will allow structural diversification of complex molecules as well as a structural editing approach to provide homologous scaffolds to bioactive molecules. Lastly, primary amines are surprisingly widely available, far more so than alkyl halides or even carboxylic acids, no doubt due to the ubiquity and importance of amide bond constructions. We will develop a complementary strategy that will use the C-N bond as a functional group handle in cross-coupling chemistry. All of these methods are designed to facilitate drug design and discovery in the pursuit of more efficacious treatments for human diseases. The specific goals of this research are as follows: 1) Site-Selective Remote Functionalization of Aliphatic Amines 2) Selective α-Functionalization of Tertiary Alkylamines 3) Deaminative Functionalization of Primary Amines PHS 398/2590 (Rev. 09/04) Page Continuation Format Page

首席研究员/项目总监（最后、第一、中间）：Rovis、Tomislav 脂肪胺及其衍生物的选择性官能化 脂肪胺在药物化合物中普遍存在，推动了对脂肪胺的重要研究 含氮原子分子的合成和功能化传统策略使用官能团。 我们一直在从事一项使用常驻C-H键的研究项目。 并将它们直接转化为感兴趣的功能，这是胺衍生化的主要挑战， 因此，在上一个资助期间提出了一些战略。 并取得了广泛的成功。 在下一个资助期内，我们将扩大反应体系、激活位置和 我们将开发对脂肪胺中的 C-H 键进行芳基化的方法，以实现对现有方法的补充。 与烯烃双官能化类似，邻位 C-H 键双官能化，同样具有完整的位置 选择性并使用地球丰富的金属盐来激活胺的远端C-H键。 方法旨在提供一种将叔胺上难以接近的C-H键官能化的方法， 许多 FDA 批准的药物的共同成分将允许复杂的结构多样化。 分子以及结构编辑方法，为生物活性分子提供同源支架。 最后，令人惊讶的是，伯胺的用途广泛，远远超过烷基卤化物甚至羧基胺 毫无疑问，由于酰胺键结构的普遍性和重要性，我们将开发一种。 互补策略，将使用 C-N 键作为交叉偶联化学中的官能团句柄。 所有这些方法旨在促进药物设计和发现，以追求更有效的药物 人类疾病的治疗。 本研究的具体目标如下： 1) 脂肪胺的位点选择性远程功能化 2) 叔烷基胺的选择性α-官能化 3) 伯胺的脱氨基功能化 PHS 398/2590（修订版 09/04） 页面延续 格式页面