期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 12, 页码 6357-6361出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202014196
关键词
chemoselectivity; deoxygenative deuteration; drug molecules; electrocatalysis; reduction
资金
- National Natural Science Foundation of China [21972094, 21672163]
- Guangdong Special Support Program, Pengcheng Scholar program
- Shenzhen Innovation Program [JCYJ20190808142001745]
This method involves the palladium-catalyzed introduction of deuterium into carbon-oxygen bonds in alcohols and ketones using D-2 balloon at room temperature, showcasing a practical synthesis of deuterated pharmaceuticals and chemicals. Its advantages include mild conditions, broad scope, and high chemoselectivity. By utilizing electrocatalytic D2O-splitting, D-2 can be supplied on demand, enabling precise incorporation of deuterium in pharmaceuticals in a sustainable and practical way.
Site-specific incorporation of deuterium into drug molecules to study and improve their biological properties is crucial for drug discovery and development. Herein, we describe a palladium-catalyzed room-temperature deuterogenolysis of carbon-oxygen bonds in alcohols and ketones with D-2 balloon for practical synthesis of deuterated pharmaceuticals and chemicals with benzyl-site (sp(3) C-H) D-incorporation. The highlights of this deoxygenative deuteration strategy are mild conditions, broad scope, practicability and high chemoselectivity. To enable the direct use of D2O, electrocatalytic D2O-splitting is adapted to in situ supply D-2 on demand. With this system, the precise incorporation of deuterium in the metabolic position (benzyl-site) of ibuprofen is demonstrated in a sustainable and practical way with D2O.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据