Room-Temperature Palladium-Catalyzed Deuterogenolysis of Carbon Oxygen Bonds towards Deuterated Pharmaceuticals.
Angew Chem Int Ed Engl
; 60(12): 6357-6361, 2021 03 15.
Article
em En
| MEDLINE
| ID: mdl-33332703
ABSTRACT
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 D2 balloon for practical synthesis of deuterated pharmaceuticals and chemicals with benzyl-site (sp3 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 D2 O, electrocatalytic D2 O-splitting is adapted to inâ
situ supply D2 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 D2 O.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paládio
/
Temperatura
/
Anti-Inflamatórios não Esteroides
/
Ibuprofeno
/
Deutério
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article