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

被引：15

作者：

Hou, Ke-Qiang ^{[1
]}

Chen, Xue-Ping ^{[1
]}

Huang, Yiyou ^{[1
]}

Chan, Albert S. C. ^{[1
]}

Luo, Hai-Bin ^{[1
]}

Xiong, Xiao-Feng ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Guangzhou, Peoples R China

来源：

ORGANIC LETTERS | 2020年 / 22卷 / 02期

基金：

中国国家自然科学基金;

关键词：

DIELS-ALDER REACTIONS; 4+2 CYCLOADDITION; DESIGN; ALKYLATION; COUMARINS; CATALYSIS; DIENES;

D O I：

10.1021/acs.orglett.9b04355

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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 mu M).

引用

页码：584 / 588

页数：5

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