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Asperflavipine A: A Cytochalasan Heterotetramer Uniquely Defined by a Highly Complex Tetradecacyclic Ring System from Aspergillus flavipes QCS12
Author(s) -
Zhu Hucheng,
Chen Chunmei,
Tong Qingyi,
Yang Jing,
Wei Guangzheng,
Xue Yongbo,
Wang Jianping,
Luo Zengwei,
Zhang Yonghui
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201701125
Subject(s) - heterotetramer , stereochemistry , cycloaddition , chemistry , ring (chemistry) , catenation , dna , biochemistry , protein subunit , organic chemistry , gene , catalysis
Asperflavipines A ( 1 ) and B ( 2 ), two structurally complex merocytochalasans, were isolated from Aspergillus flavipes . Asperflavipine A ( 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. Asperflavipine B ( 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).