Discovery, total syntheses and potent anti-inflammatory activity of pyrrolinone-fused benzoazepine alkaloids Asperazepanones A and B from Aspergillus candidus

• DOI: 10.1038/s42004-022-00696-2
• Publication Date: 2022-07-06T23:05:10Z
• Authors: 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
• Keywords: Anti-inflammatory; Natural product; Tricyclic; Malonate

Abstract Natural products are well established as an important resource and play role in drug discovery. Here, two pyrrolinone-fused benzoazepine alkaloids, (+)-asperazepanones A ( 1 ) B 2 with a 6/7/5 ring system, together the artifact (−)-asperazepanone ), were isolated from coral-derived Aspergillus candidus fungus. Their structures including absolute configurations elucidated by extensive spectroscopic methods, single crystal X-ray diffraction, ECD calculations. Furthermore, total syntheses of (±)- have been achieved starting commercially L-aspartic acid diethyl ester hydrochloride monoethyl malonate 7 8 steps, respectively. The key step was intramolecular Friedel-Crafts reaction to build unique tricyclic skeleton. Interestingly, (+)- not only showed obviously inhibitory activity against NO production, but also inhibited potent LPS-induced expression TNF-α IL-6 at concentration 0.1 μM. It thus represents potentially promising lead for anti-inflammatory