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Asymmetric Total Synthesis and Biological Evaluation of the Natural PDE4 Inhibitor Toddacoumalone

Ke-Qiang Hou, Xue-Ping Chen, Yiyou Huang, Albert S C Chan, Hai-Bin Luo, Xiao-Feng Xiong

Org Lett. 2020 Jan 17;22(2):584-588.

PMID: 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).

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP107868 3-Methylcrotonaldehyde 3-Methylcrotonaldehyde 107-86-8 Price
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