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: 9901587
• 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 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901587
• 关键词: Address; 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 现代药物发现要求越来越复杂的物质的快速和模块化组装。 具有绝大多数的药物相关分子具有氮功能，有910个1086 FDA小 分子药物至少含有一种N原子。在零售销售的前200名药物（2012年）中，有73％是小的 基于分子。其中，有67％的脂肪族胺被定义为具有氮的一部分或 苯胺系统。直接在C-H键处官能化基于胺的前体是一个重要的问题。 该建议描述了旨在解决此问题的几种策略 实现目标的策略。由此产生的产品将促进药物发现的空间 在生物活性剂中可见的常见基序，从抗生素，抗抑郁药等等。 其他的。这项研究的具体目标如下： 1）开发一种通过1,5氢原子转移对胺函数化的统一方案； 2）利用氮上的不同指导组来达到完整的位点选择性； 3）通过合并钴和光毒素催化扩大自由基夫妇。 该科学的长期影响是使化学家能够快速组装出高的复杂结构 效率。