Chinese Journal of Organic Chemistry >
Synthesis and Antitumor Activity of Lycogarubin C and Lycogalic Acid
Received date: 2013-11-18
Revised date: 2013-12-02
Online 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.
Chen Wang , Hao Huilin , Zhang Chenlu , Shen Yuemao . Synthesis and Antitumor Activity of Lycogarubin C and Lycogalic Acid[J]. Chinese Journal of Organic Chemistry, 2014 , 34(4) : 797 -803 . DOI: 10.6023/cjoc201311030
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