Direct Bioisostere Replacement Enabled by Metallaphotoredox Deoxydifluoromethylation.
J Am Chem Soc
; 146(8): 5067-5073, 2024 02 28.
Article
en En
| MEDLINE
| ID: mdl-38365186
ABSTRACT
The replacement of a functional group with its corresponding bioisostere is a widely employed tactic during drug discovery campaigns that allows medicinal chemists to improve the ADME properties of candidates while maintaining potency. However, the incorporation of bioisosteres typically requires lengthy de novo resynthesis of potential candidates, which represents a bottleneck in their broader evaluation. An alternative would be to directly convert a functional group into its corresponding bioisostere at a late stage. Herein, we report the realization of this approach through the conversion of aliphatic alcohols into the corresponding difluoromethylated analogues via the merger of benzoxazolium-mediated deoxygenation and copper-mediated C(sp3)-CF2H bond formation. The utility of this method is showcased in a variety of complex alcohols and drug compounds.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Descubrimiento de Drogas
Idioma:
En
Revista:
J Am Chem Soc
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos