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Asperchalasine A, a Cytochalasan Dimer with an Unprecedented Decacyclic Ring System, from Aspergillus flavipes
Author(s) -
Zhu Hucheng,
Chen Chunmei,
Xue Yongbo,
Tong Qingyi,
Li XiaoNian,
Chen Xintao,
Wang Jianping,
Yao Guangmin,
Luo Zengwei,
Zhang Yonghui
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201506264
Subject(s) - dimer , stereochemistry , chemistry , ring (chemistry) , cell cycle , cyclin dependent kinase 6 , two dimensional nuclear magnetic resonance spectroscopy , cyclin dependent kinase 2 , cell , biochemistry , organic chemistry
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‐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.