Selective Functionalization of Aliphatic Amines and Derivatives

脂肪胺及其衍生物的选择性官能化

• 批准号: 9398254
• 负责人: Tomislav Rovis
• 金额: $ 26.86万
• 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 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9398254
• 关键词: Address; Amination; Amines; Aniline; Antibiotics; Antidepressive Agents; Biological; Catalysis; Cobalt; Complex; Couples; Goals; Health; Hydrogen; Hydrogen Bonding; Methodology; Methods; Modernization; Nitrogen; Pharmaceutical Preparations; Principal Investigator; Protocols documentation; Research; Sales; Science; Site; Structure; System; Therapeutic Agents; Ursidae Family; base; drug discovery; programs; small molecule

Project Summary Modern drug discovery mandates the rapid and modular assembly of increasingly complex substances. Medicinally relevant molecules overwhelmingly bear nitrogen functionality with 910 of 1086 FDA small molecule drugs contain at least one N-atom. Of the Top 200 drugs by retail sales (2012), 73% are small- molecule based. Of these, 67% bear an aliphatic amine defined as having nitrogen not part of a heterocycle or aniline system. Functionalizing simple amine based precursors directly at C-H bonds is a significant problem. This proposal describes several strategies aimed at addressing this problem relying o complementary strategies to achieve the goal. The resultant products will facilitate the pace of drug discovery, with the common motifs visible in biologically active agents ranging from antibiotics, antidepressants among many others. The specific goals of this research are as follows: 1) Develop a unified protocol for δ functionalization of amines by 1,5 hydrogen atom transfer; 2) Exploit different directing groups on nitrogen to achieve complementary site selectivity; 3) Expand radical couples by merging cobalt and photoredox catalysis. The long-term impact of this science is to enable chemists to rapidly assemble complex structures with high efficiency.

项目摘要 现代药物发现要求快速和模块化组装日益复杂的物质。 医学相关分子绝大多数具有氮官能团，1086种FDA小分子中有910种具有氮官能团， 分子药物含有至少一个N原子。在零售额最高的200种药物中（2012年），73%是小型药物- 基于分子其中，67%带有定义为具有不是杂环的一部分的氮的脂族胺，或 苯胺体系直接在C-H键处官能化简单的基于胺的前体是一个重要的问题。 该提案描述了旨在解决这一问题的几项战略， 实现目标的战略。由此产生的产品将促进药物发现的步伐， 常见的图案可见于生物活性剂，包括抗生素，抗抑郁药，其中许多 他人本研究的具体目标如下： 1)开发通过1，5氢原子转移进行胺的δ官能化的统一方案; 2)利用氮上的不同导向基团实现互补位点选择性; 3)通过合并钴和光氧化还原催化来扩展自由基对。 这门科学的长期影响是使化学家能够快速组装复杂的结构， 效率