New natural products from the sponge-derived fungus Aspergillus niger
New natural products from the sponge-derived fungus Aspergillus niger
复制标题
DOI：
10.1021/np030551d
复制
发表时间：
2004-09-01
影响因子：
5.1
通讯作者：
Bringmann, G
中科院分区：
文献类型：
--
作者：
Hiort, J;Maksimenka, K;Bringmann, G
从地中海海绵达角Axinella damicornis中分离的静态培养黑曲霉（Aspergillus niger）的EtOAc提取物分离得到8种次级代谢物，其中7种化合物（2-8）被证明是新的天然产物，而一种被鉴定为已知的真菌色素cycloeucomelone(1)。新化合物包括3,3'-双香豆素双香豆素(2)，结构不寻常的4-苄基- 1h -吡啶-6- 1衍生物aspernigins A和B(3和4)，以及pyranonigins A- d(5-8)，后者具有迄今为止自然界中前所未有的新型pyrano[3,2- B]吡咯骨架。所有的结构都是在广泛的一维和二维NMR研究（H-1, C-13， COSY， HMQC， HMBC， NOE差谱）和质谱分析的基础上进行的。对于两个手性分子4和5，通过圆二色性（CD）光谱的量子化学计算建立了它们的绝对构型。在每种情况下，两种独立的方法，即考虑分子柔韧性的分子动力学方法，以及对由此获得的单个CD谱计算的玻尔兹曼加权的构象分析，都可以得到相同的结果，而无需对参考化合物报告的热学数据进行任何经验比较。双古马尼素(2)在体外对人癌细胞具有中等的细胞毒性。此外，还发现aspernigrin B(4)对谷氨酸具有较强的神经保护作用。
Fractionation of the EtOAc extract of a static culture of Aspergillus niger isolated from the Mediterranean sponge Axinella damicornis yielded eight secondary metabolites, out of which seven compounds (2-8) proved to be new natural products, whereas one was identified as the known fungal pigment cycloleucomelone (1). The new compounds included the 3,3'-bicoumarin bicoumanigrin (2), the structurally unusual 4-benzyl-1H-pyridin-6-one derivatives aspernigrins A and B (3 and 4), and pyranonigrins A-D (5-8), the latter featuring a novel pyrano[3,2-b]pyrrole skeleton hitherto unprecedented in nature. All structures were elucidated on the basis of extensive one- and two-dimensional NMR spectroscopic studies (H-1, C-13, COSY, HMQC, HMBC, NOE difference spectra) and mass spectral analysis. For the two chiral molecules 4 and 5, the absolute configurations were established by quantum chemical calculations of their circular dichroism (CD) spectra. In each case, two independent methods, i.e., a molecular dynamics approach taking into consideration the molecular flexibility, and a conformational analysis followed by Boltzmann weighting of the single CD spectra calculated for the conformers thus obtained, led to identical results without the need of any empirical comparison of chiroptical data reported for reference compounds. Bicoumanigrin (2) showed moderate cytotoxicity against human cancer cell lines in vitro. In addition, aspernigrin B (4) was found to display a strong neuroprotective effect against glutamic acid.