Title
Discovery, total syntheses and potent anti-inflammatory activity of pyrrolinone-fused benzoazepine alkaloids Asperazepanones A and B from Aspergillus candidus
Author
Li Xu, Feng-Wei Guo, Xue-Qing Zhang, Tian-Yi Zhou, Chao-Jie Wang, Mei-Yan Wei, Yu-Cheng Gu, Chang-Yun Wang & Chang-Lun Shao
Year
2022
Journal
Communications Chemistry
Abstract
Natural products are well established as an important resource and play an important role in drug discovery. Here, two pyrrolinone-fused benzoazepine alkaloids, (+)-asperazepanones A (1) and B (2) with a 6/7/5 ring system, together with the artifact (−)-asperazepanone A (1), were isolated from the coral-derived Aspergillus candidus fungus. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, single crystal X-ray diffraction, and ECD calculations. Furthermore, total syntheses of (±)-1 and (±)-2 have been achieved starting from the commercially L-aspartic acid diethyl ester hydrochloride and monoethyl malonate in 7 and 8 steps, respectively. The key step in the syntheses was an intramolecular Friedel-Crafts reaction to build the unique tricyclic skeleton. Interestingly, (+)-2 not only showed obviously inhibitory activity against NO production, but also inhibited potent LPS-induced expression of TNF-α and IL-6 at the concentration of 0.1 μM. It thus represents a potentially promising lead for anti-inflammatory drug discovery.
Full Article
Instrument
J-715, P-1020
Keywords
drug, discovery, anti-inflammatory,