海洋真菌Penicillium sclerotiorum GZU-XW03-2来源的杂萜类成分研究

Rerearch on meroterpenoids from marine-derived fungus Penicillium sclerotiorum GZU-XW03-2

目的为获得结构多样、活性显著的次级代谢产物,对1株海洋来源真菌Penicillium sclerotiorum GZUXW03-2的化学成分进行研究。方法菌种经过活化后,经大米固体培养基大规模发酵后的菌丝体用甲醇浸提,旋干后,用水混悬,接着用乙酸乙酯萃取得粗提物。乙酸乙酯萃取物经硅胶色谱、凝胶色谱、反相色谱及高效液相色谱等柱色谱分离,对获得的单体成分采用核磁共振(NMR)、单晶衍射、电子圆二色谱(ECD)、高分辨质谱(HRMS)等手段进行鉴定,结合相关文献数据从而确定化合物结构。结果从乙酸乙酯部位共分离获得6个杂萜化合物,依次为preaustinoid A6(1)、1-oxymethyl-hydropreaustinoid A1(2)、preaustinoid A1(3)、miniolutelide A(4)、miniolutelide B(5)、chrysogenolide C(6)。结论以上6个化合物均属于由3,5-二甲基苔色酸(即DMOA)途径衍生合成的杂萜类化合物,并且化合物1~6均为首次从Penicillium sclerotiorum中分离获得,其中A环开环的化合物1、2在天然产物中并不常见,此前共报道此类型化合物仅4个,化合物4的单晶数据为首次报道。

Objective To obtain secondary metabolites with diverse structures and significant activities, the chemical investigations of a marine-derived fungus Penicillium sclerotiorum GZU-XW03-2 was carried out. Methods The activated fungus was cultured on rice substrate medium, the fungal mycelia were extracted with MeOH. Afterward, the EtOAc crude was obtained by means of extraction using EtOAc solvent. Then, the EtOAc crude was subjected to silica gel column chromatography, Sephadex LH-20, reverse ODS column chromatography, and high performance liquid chromatography. Subsequently, the pure compounds were isolated. Their structures were assigned with the help of nuclear magnetic resonance(NMR), X-ray crystallographic analysis, electronic circular dichroism(ECD), high-resolution mass spectrometry(HRMS) and the literature data. Results The EtOAc extract of fermentation broth of the fungus led to the isolation and characterization of six compounds, preaustinoid A6(1), 1-oxymethyl-hydropreaustinoid A1(2), preaustinoid A1(3), miniolutelide A(4), miniolutelide B(5), and chrysogenolide C(6). Conclusion All compounds belonged to meroterpenoids derived from the 3,5-dimethylorsellinic acid(DMOA) pathway, and compounds 1~6 were all isolated from the fungus Penicillium sclerotiorum for the first time. Among them, compounds 1, 2 with opened A ring were not common in natural products, only 4 compounds of this type had been reported before. Furthermore, the single crystal data of compound 4 was first reported.