AsperchalasineA, a Cytochalasan Dimer with an Unprecedented Decacyclic Ring System, from Aspergillus flavipes
AsperchalasineA, a Cytochalasan Dimer with an Unprecedented Decacyclic Ring System, from Aspergillus flavipes
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AsperchalasineA 是一种细胞松弛素二聚体，具有前所未有的十环系统，来自黄曲霉
DOI：
10.1002/anie.201506264
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发表时间：
2015-11-02
影响因子：
16.6
通讯作者：
Zhang, Yonghui
中科院分区：
文献类型：
--
作者：
Zhu, Hucheng;Chen, Chunmei;Zhang, Yonghui
从黄足曲霉（Aspergillus flavipes）的发酵液中分离得到了第一个具有独特的5/6/11/5/6/5/11/6/5十环手性中心的细胞松弛素二聚体-β-松弛素A（1）。还分离到三种生物遗传学相关的中间体，曲霉松弛素B-D（2-4）。它们的结构，包括它们的绝对构型，使用HRESIMS，NMR，ECD，分子建模和单晶X-射线衍射技术的组合进行了阐明。具有前所未有的13-氧杂四环[7.2.1.1（2，5）.0（1，6）]十三碳-8，12-二酮核心结构的化合物1是二聚体细胞松弛素生物碱的第一个实例。从共分离的化合物5和6开始描述1-4的生物遗传途径。更重要的是，1诱导显着的G1期细胞周期阻滞通过选择性抑制细胞周期蛋白A，CDK 2和CDK 6在癌细胞，但不正常，细胞，突出它作为一个潜在的选择性细胞周期调节剂对癌细胞。
AsperchalasineA (1), the first cytochalasan dimer featuring a unique decacyclic 5/6/11/5/5/6/5/11/6/5 ring system consisting of 20 chiral centers, was isolated from the culture broth of Aspergillus flavipes. Three biogenetically related intermediates, asperchalasinesB-D (2-4), were also isolated. Their structures, including their absolute configurations, were elucidated using a combination of HRESIMS, NMR, ECD, molecular modeling, and single-crystal X-ray diffraction techniques. Compound 1, which possesses an unprecedented 13-oxatetracyclo[7.2.1.1(2,5).0(1,6)]tridec-8,12-dione core structure, is the first example of a dimeric cytochalasan alkaloid. The biogenetic pathways of 1-4 were described starting from the co-isolated compounds 5 and 6. More importantly, 1 induced significant G1-phase cell cycle arrest by selectively inhibiting cyclin A, CDK2 and CDK6 in cancerous, but not normal, cells, highlighting it as a potentially selective cell cycle regulator against cancer cells.