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



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   

  1. 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
  • 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 Chuntinga,b, Bi Kaijianb, Chang Wanlinb, Ye Jib, Zhang Weidonga,b, Sun Qingyanb   

  1. 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).

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