Abstract：
Diketopiperazine alkaloids have proven the most abundant heterocyclic alkaloids up to now, which usually process diverse scaffolds and rich biological activities. In our search for bioactive diketopiperazine alkaloids from marine-derived fungi, two novel diketopiperazine alkaloids, penipiperazine A (1) and its biogenetically related new metabolite (2), together with a known analogue neofipiperzine C (3), were obtained from the strain Penicillium brasilianum. Their planar structures and absolute configurations were elucidated by extensive spectroscopic analyses, 13C NMR calculation, Marfey\'s, ECD, and ORD methods. Compound 1 featured a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system, and its plausible biogenetic pathway was also proposed. Additionally, compounds 1-3 have been tested for their inflammatory activities. 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells, suggesting they could be attracting candidate for further development as anti-inflammatory agent. KEY POINTS: • A novel diketopiperazine alkaloid featuring a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system was isolated from the marine fungus Penicillium brasilianum. • The structure of 1 was elucidated by detailed analysis of 2D NMR data, 13C NMR calculation, Marfey\'s, ECD, and ORD methods. • Compounds 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells.
摘要：
二酮哌嗪生物碱已被证明是迄今为止最丰富的杂环生物碱，它通常处理多种支架和丰富的生物活性。在我们从海洋真菌中寻找生物活性二酮哌嗪生物碱的过程中，两种新的二酮哌嗪生物碱，哌嗪A（1）及其生物相关的新代谢产物（2），连同已知的类似物新菲哌嗪C（3），从菌株巴西青霉获得。通过广泛的光谱分析阐明了它们的平面结构和绝对构型，13C核磁共振计算，Marfey\'s,ECD,和ORD方法。化合物1具有独特的6/5/6/6/5吲哚-吡嗪并-吡嗪并-吡咯系统，并提出了其合理的生物遗传途径。此外,已经测试了化合物1-3的炎症活性。1和2显著抑制LPS刺激的RAW264.7细胞NO的释放和相关促炎细胞因子的表达,这表明它们可能是进一步开发抗炎药的候选药物。关键点:•从海洋真菌巴西青霉分离出具有独特的6/5/6/6/5吲哚-吡嗪-吡嗪基-吡咯系统的新型二酮哌嗪生物碱。•通过对2DNMR数据的详细分析阐明了1的结构，13C核磁共振计算，Marfey\'s,ECD,和ORD方法。•化合物1和2显著抑制LPS刺激的RAW264.7细胞上NO的释放和相关促炎细胞因子的表达。
