Efficient Industrial Synthesis of the MDM2 Antagonist Idasanutlin via a Cu(I)-catalyzed [3+2] Asymmetric Cycloaddition.
Chimia (Aarau)
; 72(7): 492-500, 2018 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-30158012
ABSTRACT
A concise asymmetric synthesis has been developed to prepare idasanutlin, a small molecule MDM2 antagonist. Idasanutlin is currently being investigated as a potential treatment for various solid tumors and hematologic malignancies. The highly congested pyrrolidine core, containing four contiguous stereocenters, was constructed via a Cu(I)/(R)-BINAP catalyzed [3+2]-cycloaddition reaction. This optimized copper(I)-catalyzed process has been used to produce more than 1500 kg of idasanutlin. The manufacturing process will be described, highlighting the exceptionally selective and consistent cycloaddition/isomerization/hydrolysis sequence. The excellent yields, short cycle times and reduction in waste streams result in a sustainable production process with low environmental impact.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
/
Proteínas Proto-Oncogênicas c-mdm2
/
Para-Aminobenzoatos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article