Synthesis of a Tubulin Assembly Inhibitors OXi8006

doi:10.6023/cjoc201408037

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (2): 484-489.DOI: 10.6023/cjoc201408037 Previous Articles Next Articles

Notes

微管蛋白聚合抑制剂OXi8006的合成新方法

刘春廷^a,b, 毕凯健^b, 畅婉琳^b, 叶霁^b, 张卫东^a,b, 孙青龑^b

a 江西中医药大学药学院南昌 330004;
b 第二军医大学药学院上海 200433

收稿日期:2014-08-29 修回日期:2014-10-21 发布日期:2014-10-23
通讯作者: 孙青龑 E-mail:sqy_2000@163.com
基金资助:
国家自然科学基金(No. 81230090)、上海市重点学科建设(No. B906)资助项目.

Synthesis of a Tubulin Assembly Inhibitors OXi8006

Liu Chunting^a,b, Bi Kaijian^b, Chang Wanlin^b, Ye Ji^b, Zhang Weidong^a,b, Sun Qingyan^b

a College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004;
b College of Pharmacy, The Second Military Medical University, Shanghai 200433

Received:2014-08-29 Revised:2014-10-21 Published:2014-10-23
Supported by:
Project supported by the National Natural Science Foundation of China (No. 81230090), the Shanghai Leading Academic Discipline Project (No. B906).

1. Synthesis of a Tubulin Assembly Inhibitors OXi8006.PDF(2106KB)

Abstract

2-(3'-Hydroxy-4'-methoxyphenyl)-3-(3",4",5"-trimethoxybenzoyl)-6-methoxyindole (OXi8006) was found to be a strong inhibitors of tubulin assembly and showed excellent anticancer activity (IC₅₀=1.1 μmol/L). Reported synthetic method of OXi8006 suffered from some drawbacks, such as long steps and low overall yields. Therefore, developing more efficient and practical protocols to synthesize OXi8006 is highly desirable. Firstly, we prepared aryl acetylene from commercially available isovanillin in three steps. Then the aryl acetylene was converted to diaryl acetylene ketone by reacting with 3,4,5-trimethoxybenzaldehyde via nucleophilic addition and oxidation reaction. The key step of 2-aryl-3-aroyl-indole construction was carried out between diaryl acetylenic ketone and o-iodo aniline by performing aza-Michael addition and subsequent intramolecular Heck reaction. The yield of developed synthesis over six steps is 20%.

Key words: tubulin assembly inhibitors, OXi8006, aza-Michael addition, Heck reaction

Cite this article

Liu Chunting, Bi Kaijian, Chang Wanlin, Ye Ji, Zhang Weidong, Sun Qingyan. Synthesis of a Tubulin Assembly Inhibitors OXi8006[J]. Chin. J. Org. Chem., 2015, 35(2): 484-489.

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微管蛋白聚合抑制剂OXi8006的合成新方法

Synthesis of a Tubulin Assembly Inhibitors OXi8006

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