Asymmetric total synthesis and anti-hepatocellular carcinoma profile of enantiopure euphopilolide and jolkinolide E.
Asymmetric total synthesis and anti-hepatocellular carcinoma profile of enantiopure euphopilolide and jolkinolide E.
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DOI：
10.1016/j.bioorg.2023.106688
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发表时间：
2023-06
影响因子：
5.1
通讯作者：
X. Li;Jian Chen;Kaixuan Luo;Yishan Guo;Yongxing Deng;Xianli Li;Wenjing Chen;Zunnan Huang;Jianqiang Liu;Zhengzhi Wu;Cheng Tao
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文献类型：
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作者：
X. Li;Jian Chen;Kaixuan Luo;Yishan Guo;Yongxing Deng;Xianli Li;Wenjing Chen;Zunnan Huang;Jianqiang Liu;Zhengzhi Wu;Cheng Tao
本文报道了Euphopilicate（1）和jolkinicate（2）[（+）-和（-）-1，（+）-和（-）-2]两种对映体的灵活不对称合成。该合成以分子内oxa-Pauson-Khand反应（o-PKR）为特征，以迅速构建具有挑战性的四环[6.6.6.5]松香烷型二萜框架，优雅地展示了利用明智选择的合适手性池支架的o-PKR合成方法的复杂性生成特征。此外，评价了合成的（-）-大戟碱（1）、（-）-jolkinaseE（2）及其类似物的抗肝细胞癌（HCC）活性。我们发现（-）-大戟碱（1）和（-）-jolkinaseE（2）抑制HCC细胞的增殖并诱导凋亡。这些发现为进一步研究松香烷内酯衍生物的药理作用奠定了良好的基础，并为开发天然来源的抗肝癌小分子药物提供了有价值的见解。
A flexible asymmetric synthesis of both enantiomers of euphopilolide (1) and jolkinolide E (2) [(+)-and (−)-1, (+)-and (−)-2] has been accomplished. This synthesis features an intramolecularoxa-Pauson-Khand reaction (o-PKR) to expeditiously construct the challenging tetracyclic [6.6.6.5] abietane-type diterpene framework, elegantly showcasing the complexity-generating features ofo-PKR synthetic methodology leveraging on a judiciously chosen suitable chiral pool scaffold. Furthermore, the anti-hepatocellular carcinoma (HCC) activity of synthetic (−)-euphopilolide (1), (−)-jolkinolide E (2) and their analogues was evaluated. We found that (−)-euphopilolide (1) and (−)-jolkinolide E (2) inhibited the proliferation and induced apoptosis in HCC cells. These findings lay a good foundation for further pharmacology studies of abietane lactone derivatives and provide valuable insight for the development of anti-HCC small molecule drug of natural product origin.