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.

天然产物被认为是一种重要资源，在药物发现中发挥着重要作用。在这里，两种吡咯啉酮稠合的苯并氮杂生物碱，具有 6/7/5 环系统的 (+)-asperazepanones A ( 1 ) 和 B ( 2 )，以及人工产物 (−)-asperazepanone A ( 1 )，是从源自珊瑚的白曲霉真菌。通过广泛的光谱方法、单晶 X 射线衍射和 ECD 计算阐明了它们的结构（包括绝对构型）。此外，以商业L-天冬氨酸二乙酯盐酸盐和丙二酸单乙酯为原料，分别经过7步和8步实现了(±) -1和(±) -2的全合成。合成的关键步骤是分子内傅克反应，以构建独特的三环骨架。有趣的是，(+)- 2不仅对NO产生具有明显的抑制活性，而且在0.1 μM浓度下还能有效抑制LPS诱导的TNF-α和IL-6的表达。因此，它代表了抗炎药物发现的潜在有前途的先导。