Asperchalasine A, a Cytochalasan Dimer with an Unprecedented Decacyclic Ring System, from Aspergillus flavipes. (3rd September 2015)

• Record Type: Journal Article
• Authors: Zhu, Hucheng; Chen, Chunmei; Xue, Yongbo; Tong, Qingyi; Li, Xiao‐Nian; Chen, Xintao; Wang, Jianping; Yao, Guangmin; Luo, Zengwei; Zhang, Yonghui
• Is Part Of: Angewandte Chemie. Volume 127:Number 45(2015)
• Page Start: 13572
• Page End: 13576
• Publication Date: 2015-09-03
• Subjects: Alkaloide -- Aspergillus flavipes -- Cytochalasan -- Dimere; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201506264
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Compound1, 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 of1 –4 were described starting from the co‐isolated compounds5 and6 . 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.