Penipyridones A–F, Pyridone Alkaloids from Penicillium funiculosum

Six new pyridone alkaloids, named
penipyridones A–F (1–6), were
isolated from the fermentation broth of an Antarctic moss-derived
fungus, Penicillium funiculosum GWT2-24. Their structures
were elucidated from extensive NMR and MS data. Although they possess
the same major chromophore and some of them presented almost mirror
ECD spectra, their absolute configurations were found to be uniformly S, as evidenced by X-ray single-crystal diffraction analysis,
stereocontrolled total synthesis, and chemical conversions. TDDFT-ECD
calculations of compounds 3 and 6 revealed
that subtle conformational changes are responsible for the significantly
different ECD curves. None of the compounds were cytotoxic (IC50 > 50 μM), while compounds 1, 2, 5, and 7 elicited lipid-lowering
activity in HepG2 hepatocytes.

从南极苔藓来源的真菌Penicillium funiculosum GWT2-24的发酵液中成功分离出六种新的吡啶醇类生物碱，分别命名为penipyridones A–F (1–6)。通过对大量的核磁共振（NMR）和质谱（MS）数据进行解析，阐明了其结构。尽管它们拥有相同的主体发色团，其中某些化合物的电子圆二色光谱（ECD）几乎呈镜像关系，但通过X射线单晶衍射分析、立体控制的全合成以及化学转化实验，发现它们的绝对构型均为S型。TDDFT-ECD计算揭示了化合物3和6中微妙的构象变化是导致其ECD曲线显著差异的原因。所有化合物均不具有细胞毒性（IC50 > 50 μM），而化合物1、2、5和7在HepG2肝细胞中表现出降脂活性。