Asperchalasine A,a Cytochalasan Dimer with an Unprecedented Decacyclic Ring System,from Aspergillus flavipes |
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| Authors: | Dr Hucheng Zhu Dr Chunmei Chen Dr Yongbo Xue Dr Qingyi Tong Dr Xiao‐Nian Li Xintao Chen DrProf Jianping Wang ProfDr Guangmin Yao Dr Zengwei Luo ProfDr Yonghui Zhang |
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| Institution: | 1. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China);2. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204 (China) |
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| Abstract: | Asperchalasine A ( 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, asperchalasines B–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‐oxatetracyclo7.2.1.12,5.01,6]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. |
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| Keywords: | alkaloids Aspergillus flavipes cytochalasan dimers |
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