Asymmetric Total Synthesis and Biological Evaluation of the Natural PDE4 Inhibitor Toddacoumalone.
Org Lett
; 22(2): 584-588, 2020 01 17.
Article
em En
| MEDLINE
| ID: mdl-31904969
ABSTRACT
We describe herein the first asymmetric total synthesis and biological evaluation of the natural PDE4 inhibitor toddacoumalone and its stereoisomers. The key step of the total synthesis is a formal asymmetric [4 + 2] cycloaddition reaction catalyzed by chiral secondary amine catalysts. A variety of pyranoquinolinones and 3-methylcrotonaldehyde are well tolerated under the optimized reaction conditions, which paved the way for further SAR studies. Further biological evaluation showed 1a' with the best PDE4 inhibitory activity (IC50 = 0.18 µM).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Cumarínicos
/
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4
/
Inibidores da Fosfodiesterase 4
Limite:
Humans
Idioma:
En
Revista:
Org Lett
Ano de publicação:
2020
Tipo de documento:
Article