Synthesis of Wogonin, a Natural Product with Anticancer Activity

doi:10.6023/cjoc201604057

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (12): 2960-2964.DOI: 10.6023/cjoc201604057 Previous Articles Next Articles

ARTICLE

抗肿瘤天然产物汉黄芩素的合成

袁虎^a, 叶霁^b, 陈浩^b, 赵增^b, 李玉柱^a, 张卫东^a,b, 孙青龑^a

a 中国医药工业研究总院上海 200040;
b 第二军医大学药学院上海 200433

收稿日期:2016-04-27 修回日期:2016-06-21 发布日期:2016-08-10
通讯作者: 张卫东, 孙青龑 E-mail:sqy_2000@163.com;wdzhangy@hotmail.com
基金资助:
长江学者奖励计划、国家自然科学基金（Nos. 81520108030，81573318，81373301，1302658）、上海市重点学科建设（No. B906）和上海活性天然产物制备工程研究中心（No. 10DZ2251300）资助项目.

Synthesis of Wogonin, a Natural Product with Anticancer Activity

Yuan Hu^a, Ye Ji^b, Chen Hao^b, Zhao Zeng^b, Li Yuzhu^a, Zhang Weidong^a,b, Sun Qingyan^a

a Shanghai Institute of Pharmaceutical Industry, Shanghai 200040;
b Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433

Received:2016-04-27 Revised:2016-06-21 Published:2016-08-10
Supported by:
Project supported by the Professor of Chang Jiang Scholars Program, the National Natural Science Foundation of China (Nos. 81520108030, 81573318, 81373301, 1302658), the Shanghai Leading Academic Discipline Project (No. B906), the Shanghai Engineering Research Center for the Preparation of Bioactive Natural Products (No. 10DZ2251300).

1. Synthesis of Wogonin, a Natural Product with Anticancer Activity.PDF(1153KB)

Abstract

Wogonin (5,7-dihydroxy-8-methoxyflavone) is an active component isolated from the Traditional Chinese Medicine (TCM) Huang Qin, which exhibits significant anti-tumor activity via a unique mechanism. The reported chemical synthesis of wogonin suffered either from low overall yield, harsh reaction conditions or from noncommercially available starting materials. In this paper, a new synthesis of wogonin was achieved via Claisen-Schmidt condensation, cyclization, iodination at C-8 position of flavone, borylation of sterically hindered aryl iodides, oxidation of boronic esters, methylation and debenzylation reaction using 2,4-dibenzyloxy-6-hydroxy phenylacetone and benzaldehyde as the starting materials, which provided gram-scale wogonin in >70% overall yield. The total synthesis employs mild reaction conditions and conventional flash column chromatography is not needed for purification, which makes it suitable for large-scale production. The efficient and flexible entry should offer opportunities for further modification and chemical biology investigations.

Key words: anticancer, wogonin, borylation, synthesis

Cite this article

Yuan Hu, Ye Ji, Chen Hao, Zhao Zeng, Li Yuzhu, Zhang Weidong, Sun Qingyan. Synthesis of Wogonin, a Natural Product with Anticancer Activity[J]. Chin. J. Org. Chem., 2016, 36(12): 2960-2964.

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抗肿瘤天然产物汉黄芩素的合成

Synthesis of Wogonin, a Natural Product with Anticancer Activity

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