Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (4): 797-803.DOI: 10.6023/cjoc201311030 Previous Articles     Next Articles


Lycogarubin C和Lycogalic Acid的化学合成及抗肿瘤活性研究

陈旺, 郝慧琳, 张晨露, 沈月毛   

  1. 山东大学药学院 济南 250012
  • 收稿日期:2013-11-18 修回日期:2013-12-02 发布日期:2013-12-13
  • 通讯作者: 沈月毛
  • 基金资助:

    国家重点基础研究发展计划(973 计划,No. 2010CB833802)、国家自然科学基金(Nos. 81273384,90913024)和国家杰出青年科学基金(No. 30325044)资助项目.

Synthesis and Antitumor Activity of Lycogarubin C and Lycogalic Acid

Chen Wang, Hao Huilin, Zhang Chenlu, Shen Yuemao   

  1. School of Pharmaceutical Sciences, Shandong University, Jinan 250012
  • Received:2013-11-18 Revised:2013-12-02 Published:2013-12-13
  • Supported by:

    Project supported by the Major State Basic Research Development Program of China (973 Program, No. 2010CB833802), the National Natural Science Foundation of China (Nos. 81273384, 90913024) and the National Science Fund for Distinguished Young Scholars (No. 30325044).

Lycogarubin C and lycogalic acid were first isolated independently by Steglich and Akazawa from Lycogala epidendrum in 1994. Lycogarubin C showed a potential cytotoxic activity. Lycogalic acid is an inhibitor of Hes1 dimmer of helix-loop-helix (bHLH) transcriptional repressor factor. Lycogalic acid is also the key intermediate in the biosynthesis of indolo[2,3-a]carbazole alkaloids that exhibit broad spectrum of bioactivity. Two efficient synthetic pathways of lycogarubin C and lycogalic acid were completed in this study. The first pathway included eight steps started from the commercially available indole and pyrrole to produce lycogarubin C with an overall yield of 27%. The second pathway was completed in seven steps with an overall yield of 25%. The key reactions are palladium-catalyzed Suzuki-Miyaura coupling of bis-iodo or bis-triflate derivative and indolboronic acid derivatives and Hinsberg-type synthesis of dimethyl N-benzyl-3,4-dihydroxypyrrole-2,5-dicarboxylate, respectively. Treatment of lycogarubin C with sodium hydroxide in ethanol under refluxing followed by acidification afforded lycogalic acid quantitatively. Lycogarubin C and lycogalic acid showed the antiproliferative activities against four human tumor cell lines of MDA-MB-231, A549, HeLa and PC3. Further study showed that lycogarubin C inhibited the activity of DNA topoisomerase 2.

Key words: lycogarubin C, lycogalic acid, Suzuki-Miyaura coupling, DNA topoisomerase 2