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Epicochalasines A and B: Two Bioactive Merocytochalasans Bearing Caged Epicoccine Dimer Units from Aspergillus flavipes
Author(s) -
Zhu Hucheng,
Chen Chunmei,
Tong Qingyi,
Li XiaoNian,
Yang Jing,
Xue Yongbo,
Luo Zengwei,
Wang Jianping,
Yao Guangmin,
Zhang Yonghui
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201511315
Subject(s) - stereocenter , dimer , chemistry , stereochemistry , nucleophile , ring (chemistry) , apoptosis , biochemistry , organic chemistry , enantioselective synthesis , catalysis
Two bioactive merocytochalasans, epicochalasines A ( 1 ) and B ( 2 ), a new class of cytochalasans bearing unexpected scaffolds consisting of fused aspochalasin and epicoccine dimer moieties, were isolated from the liquid culture broth of Aspergillus flavipes . Both 1 and 2 possess a hendecacyclic 5/6/11/5/6/5/6/5/6/6/5 ring system containing an adamantyl cage and as many as 19 stereogenic centers; however, the fusion patterns of 1 and 2 differ greatly, thus resulting in different carbon skeletons. The absolute configurations of 1 and 2 were determined by X‐ray diffraction and calculated ECD, respectively. The biogenetic pathways of 1 and 2 are proposed to involve Diels–Alder and nucleophilic addition reactions. Both 1 and 2 induced significant G2/M‐phase cell‐cycle arrest. Furthermore, we found that merocytochalasans induce apoptosis in leukemia cells through the activation of caspase‐3 and the degradation of PARP.