AsperflavipineA: A Cytochalasan Heterotetramer Uniquely Defined by a Highly Complex Tetradecacyclic Ring System from Aspergillus flavipes QCS12
AsperflavipineA: A Cytochalasan Heterotetramer Uniquely Defined by a Highly Complex Tetradecacyclic Ring System from Aspergillus flavipes QCS12
复制标题
AsperflavipineA：由来自黄曲霉 QCS12 的高度复杂的十四环系统独特定义的 Cytochalasan 异四聚体
DOI：
10.1002/anie.201701125
复制
发表时间：
2017-05-02
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（AspergillusflavipinesA）中分离得到两种结构复杂的部分细胞松弛素（mercytochalasans），即黄足曲霉黄素A（1）和黄足曲霉黄素B（2）。α-黄维平A（1）含有两个细胞松弛素部分和两个epicoccine部分，是第一个被发现的细胞松弛素异源四聚体。它由5/6/11/5/6/5/6/5/6/5/5/11/6/5稠合十四环和三个连续桥环系统唯一定义。α-黄素平B（2）是一种细胞松弛素异三聚体，含有一个细胞松弛素和两个epicoccine部分，具有5/6/11/5/5/6/5/6/5九环体系。假设的1和2的生物合成提出涉及Diels-Alder和[3+2]环加成反应的关键步骤，并揭示了无与伦比的可塑性merocytochalasans的生物合成。1的存在为细胞松弛素家族的多样性增加了一个新的维度。化合物1显示出中等的细胞毒性，并通过激活半胱天冬酶-3和降解聚（ADP-核糖）聚合酶（PARP）诱导Jurkat、NB 4和HL 60细胞的凋亡。
AsperflavipinesA (1) and B (2), two structurally complex merocytochalasans, were isolated from Aspergillus flavipes. AsperflavipineA (1), which contains two cytochalasan moieties and two epicoccine moieties, is the first cytochalasan heterotetramer to be discovered. It is uniquely defined by 5/6/11/5/6/5/6/5/6/5/5/11/6/5 fused tetradecacyclic rings with three continuous bridged ring systems. AsperflavipineB (2) is a cytochalasan heterotrimer containing a cytochalasan and two epicoccine moieties with a 5/6/11/5/5/6/5/6/5 nonacyclic ring system. The hypothetical biosynthesis of 1 and 2 is proposed to involve Diels-Alder and [3+2] cycloaddition reactions as key steps and reveals unparalleled plasticity in the biosynthesis of merocytochalasans. The existence of 1 adds a new dimension to the diversity of the cytochalasan family. Compound 1 showed moderate cytotoxicity and induced apoptosis in Jurkat, NB4, and HL60 cells through the activation of caspase-3 and degradation of poly(ADP-ribose) polymerase (PARP).