Epicochalasines A and B: Two Bioactive Merocytochalasans Bearing Caged Epicoccine Dimer Units from Aspergillus flavipes. (2nd February 2016)

• Record Type: Journal Article
• Authors: Zhu, Hucheng; Chen, Chunmei; Tong, Qingyi; Li, Xiao‐Nian; Yang, Jing; Xue, Yongbo; Luo, Zengwei; Wang, Jianping; Yao, Guangmin; Zhang, Yonghui
• Is Part Of: Angewandte Chemie. Volume 128:Number 10(2016)
• Page Start: 3547
• Page End: 3551
• Publication Date: 2016-02-02
• Subjects: Alkaloide -- Biologische Aktivität -- Pilzliche Naturstoffe -- Polycyclen -- Strukturaufklärung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201511315
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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 . Both1 and2 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 of1 and2 differ greatly, thus resulting in different carbon skeletons. The absolute configurations of1 and2 were determined by X‐ray diffraction and calculated ECD, respectively. The biogenetic pathways of1 and2 are proposed to involve Diels–Alder and nucleophilic addition reactions. Both1 and2 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.