Stereoselective Synthesis and Biological Evaluation of ent-Asperolide C and its Analogues

被引：5

作者：

Xin, Zhengyuan ^{[1
]}

Lu, Yunlong ^{[1
,3
]}

Song, Zhiqiang ^{[1
]}

He, Yuchen ^{[1
]}

Li, Jiabin ^{[2
]}

Lin, Kejiang ^{[1
]}

Xue, Xiaowen ^{[1
]}

机构：

[1] China Pharmaceut Univ, Dept Med Chem, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Sch Sci, 639 Long Mian Da Dao, Nanjing 211198, Jiangsu, Peoples R China

[3] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2018年 / 2018卷 / 04期

关键词：

Total synthesis; Chiral pool; Natural products; Epoxidation; Synthesis design; Biological activity; IN-VITRO CYTOTOXICITY; ANDROGRAPHOLIDE DERIVATIVES; OXIDATION; ACID;

D O I：

10.1002/ejoc.201701292

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A stereoselective synthesis of ent-asperolide C and its analogues is described. A chiral-pool approach was used with a linear sequence of 10 steps, starting from readily available and inexpensive andrographolide. The approach features the construction of a five-membered lactone skeleton with suitable chiral centres from andrographolide through diastereoselective epoxidation of the exocyclic double bond, and tandem oxidative cleavage of the C-14=C-15 double bond and subsequent epoxide ring opening. The stereochemistry of 8 was established by X-ray crystallographic analysis. Four analogues of ent-asperolide C were synthesized, and their biological activities were evaluated against A539 and HeLa cell lines. Compound 12 was found to show a weak to moderate antiproliferation effect against both cell lines.

引用

页码：477 / 484

页数：8

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