Enantioselective Synthesis of Oseltamivir Phosphate (Tamiflu) via the Iron-Catalyzed Stereoselective Olefin Diazidation.
J Am Chem Soc
; 140(33): 10619-10626, 2018 08 22.
Article
em En
| MEDLINE
| ID: mdl-30040881
ABSTRACT
We herein report a gram-scale, enantioselective synthesis of Tamiflu, in which the key trans-diamino moiety has been efficiently installed via an iron-catalyzed stereoselective olefin diazidation. This significantly improved, iron-catalyzed method is uniquely effective for highly functionalized yet electronically deactivated substrates that have been previously problematic. Preliminary catalyst structure-reactivity-stereoselectivity relationship studies revealed that both the iron catalyst and the complex substrate cooperatively modulate the stereoselectivity for diazidation. Safety assessment using both differential scanning calorimetry (DSC) and the drop weight test (DWT) has also demonstrated the feasibility of carrying out this iron-catalyzed olefin diazidation for large-scale Tamiflu synthesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Azidas
/
Alcenos
/
Oseltamivir
/
Ferro
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos