International Collaborative Laboratory of 2D Materials for Optoelectronic Science & Technology, Engineering Technology Research Center for 2D Materials Information Functional Devices and Systems of Guangdong Province, Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen, 518060, China.
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, China.
Angew Chem Int Ed Engl. 2021 Mar 15;60(12):6357-6361. doi: 10.1002/anie.202014196. Epub 2021 Feb 9.
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 balloon for practical synthesis of deuterated pharmaceuticals and chemicals with benzyl-site (sp 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 D O, electrocatalytic D O-splitting is adapted to in situ supply D 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 D O.
将氘原子特异性地引入药物分子中，以研究和改善其生物学特性，这对药物发现和开发至关重要。在这里，我们描述了一种钯催化的室温下醇和酮中碳-氧键的氘解反应，使用 D 气球可以实际合成具有苄位（sp C-H）氘取代的氘代药物和化学物质。这种脱氧氘代策略的突出特点是条件温和、适用范围广、实用性强和高化学选择性。为了能够直接使用 D 2 O，采用电催化 D 2 O 裂解以按需原位供应 D。有了这个系统，以可持续和实际的方式，使用 D 2 O 证明了布洛芬代谢位置（苄位）中氘的精确掺入。
