Development of Strategies for the Functionalization of Amines

胺功能化策略的开发

基本信息

批准号：
8549270
负责人：
Daniel Seidel
金额：
$ 27.17万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-21 至 2017-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The majority of pharmaceutical drugs that are essential for human health consist of nitrogen containing compounds. A particularly attractive approach to these targets is the modification of cheap and readily available amines by means of C-H bond functionalization. However, methods that accomplish this task efficiently are scarce and severely lacking in scope. Moreover, the currently known approaches typically require the use of expensive transition metal catalysts and/or oxidants. This proposal is focused on the design and development of efficient and practical methods for amine functionalization. The main goal is the ?- and ?-functionalization of amines through conceptually new and underdeveloped methods of substrate activation. A major focus is on redox-neutral approaches to C-H bond functionalization that do not require expensive oxidants or precious metal catalysts. The central theme of our proposed work is to couple an oxidative C-H bond functionalization with a productive reduction event that contributes to the formation of products by allowing for the generation of additional C-C, or C-X bonds. Our proposed reactions proceed via iminium ion, azomethine ylide and enamine intermediates that can be accessed under relatively mild conditions. In addition to targeting the rapid preparation of biologically active compounds such as epiquinamide, harmicine and quinazolinone alkaloids, our efforts will center on the development of particularly powerful reactions that rapidly generate new polycylic amines. A priority is the generation of novel structural frameworks that are absent from current drug discovery screening libraries.

描述（由申请人提供）：大多数对人类健康必不可少的药物由含氮的化合物组成。针对这些目标的一种特别有吸引力的方法是通过C-H键功能化修改便宜且随时可用的胺。但是，有效完成此任务的方法稀缺且范围严重缺乏。此外，当前已知的方法通常需要使用昂贵的过渡金属催化剂和/或氧化剂。该建议的重点是设计和开发胺功能化的有效和实用方法。主要目标是通过概念上新的且不发达的底物激活方法对胺功能化。主要重点是不需要昂贵的氧化剂或贵金属催化剂的C-H键功能化方法。我们提出的工作的中心主题是将氧化的C-H键功能化与生产性还原事件相结合，该事件通过允许产生额外的C-C或C-X键来形成产品。我们提出的反应通过亚胺离子，偶氮蛋白Ylide和烯胺中间体进行，这些反应可以在相对温和的条件下进行。除了靶向生物活性化合物（例如上氨基胺，harmicine和喹啉唑酮生物碱）之外，我们的努力还将集中在迅速产生新的多酰胺胺的特别有力反应上。一个优先的是，当前的药物发现筛选文库中没有新的结构框架。