Diphenyl Ether Derivative Rhexocerins and Rhexocercosporins from the Endophytic Fungus Rhexocercosporidium sp. Dzf14 Active against Gram-Positive Bacteria with Multidrug-Resistance

Ten new diphenyl ether polyketides, including rhexocerins A–D (1–4) and rhexocercosporins A–F (5–10), together with three known congeners (11–13), were isolated from the endophytic fungus Rhexocercosporidium sp. Dzf14 obtained from Dioscorea zingiberensis. Their structures were elucidated by analysis of NMR and HRESIMS data, and their absolute configurations were determined by quantum chemical ECD calculations and X-ray crystallography. Compounds 1–4 featured an unprecedented tetracyclic carbon skeleton (6/7/5/6). Among them, compounds 1 and 5–9 showed antibacterial activities against methicillin-resistant S. aureus T144 and vancomycin-resistant E. faecalis 10.本研究从盾叶薯蓣（Dioscorea zingiberensis）来源的内生真菌莱孢孢属（Rhexocercosporidium sp.）菌株Dzf14中，分离得到10个全新二苯醚类聚酮化合物（diphenyl ether polyketides），包括莱孢菌素A-D（rhexocerins A-D，化合物1~4）与莱孢孢菌素A-F（rhexocercosporins A-F，化合物5~10），另有3个已知同系物（congeners，化合物11~13）。通过核磁共振波谱法（Nuclear Magnetic Resonance, NMR）与高分辨电喷雾电离质谱（High Resolution Electrospray Ionization Mass Spectrometry, HRESIMS）数据分析，阐明了所有化合物的平面结构；借助量子化学电子圆二色谱（Electronic Circular Dichroism, ECD）计算与X射线晶体衍射分析（X-ray crystallography），确定了其绝对构型。化合物1~4具有前所未有的四环碳骨架（6/7/5/6）。其中，化合物1与5~9对耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus, MRSA）T144及耐万古霉素粪肠球菌（vancomycin-resistant Enterococcus faecalis, VRE）10展现出抗菌活性。