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Lycogarubin C和lycogalic acid是由Steglich和Akazawa在1994年分别独立从粘细菌Lycogala epidendrum中分离得到的海洋天然产物.Lycogarubin C有一定的细胞毒活性;lycogalic acid是螺旋-环-螺旋(Helix-Loop-Helix,bHLH)翻译阻遏因子Hes1二聚体的抑制剂.另外,lycogalic acid是吲哚[2,3-a]咔唑类生物碱的生物合成的关键中间体,吲哚[2,3-a]咔唑类生物碱有广泛的生物活性.本文报道了两条合成lycogarubin C和lycogalic acid的路线.路线一:由吲哚和吡咯出发经过8步反应以27%的收率得到lycogarubin C,其中的关键步骤是3,4-二碘-1H-吡咯-2,5-二甲酸甲酯和N-对甲基苯磺酰基-1H-吲哚-3-硼酸的Suzuki-Miyaura交叉偶联反应;路线二:由亚氨基二乙酸出发经过7步反应以25%的收率得到lycogarubin C,其中的关键步骤是N-苄基亚氨基二乙酸二甲酯和草酸二甲酯的Hinsberg反应和3,4-二三氟甲磺酸氧基-1H-吡咯-2,5-二甲酸甲酯和N-二甲基叔丁基硅基-1H-吲哚-3-硼酸的钯催化的交叉偶联反应.Lycogarubin C再经水解之后酸化得到lycogalic acid.细胞毒实验表明lycogarubin C对MDA-MB-231,A549,HeLa和PC3肿瘤细胞有一定的生长抑制作用,进一步研究表明它具有DNA拓扑异构酶2的抑制活性.
Lycogarubin C and lycogalic acid are marine natural products isolated from the myxobacteria Lycogala epidendrum by Steglich and Akazawa independently in 1994. Lycogarubin C has some cytotoxic activity; lycogalic acid is a Helix-Loop- Helix, bHLH) is an inhibitor of translation repressor Hes1 dimer.In addition, lycogalic acid is a key intermediate in the biosynthesis of indole [2,3-a] carbazole alkaloids, indole [2,3-a ] Carbazole alkaloids have a wide range of biological activity.In this paper, two routes for the synthesis of lycogarubin C and lycogalic acid were reported.Firstly, lycogarubin C was obtained in 27% yield from indole and pyrrole, The key step is Suzuki-Miyaura cross-coupling reaction of methyl 3,4-diiodo-1H-pyrrole-2,5-dicarboxylate and Np-methylbenzenesulfonyl-lH-indole-3-boronic acid; Route 2: Starting from iminodiacetic acid, lycogarubin C was obtained in 7% yield in 25% yield, the key steps of which were Hinsberg reaction of dimethyl N-benzyliminodiacetate and dimethyl oxalate and 3, 4-ditrifluoromethanesulfonic acid oxy-1H-pyrrole-2,5-dicarboxylic acid methyl ester and N-dimethyl-t-butylsilyl -1H-indole-3-boronic acid.Lycogarubin C was hydrolyzed to obtain lycogalic acid.Cytotoxicity experiments showed that lycogarubin C had significant inhibitory effect on MDA-MB-231, A549, HeLa and PC3 tumor cells Certain growth inhibition, further studies have shown that it has DNA topoisomerase 2 inhibitory activity.