Penicamins A–L, Polyoxygenated Diterpenes from Penicillium camemberti JSB-7212

Penicamins A–L (1–12), 12 highly oxygenated novel diterpenes, were obtained from the fungus Penicillium camemberti JSB-7212. Compounds 1–12 share the same 7/6/5 tricyclic skeleton as valparane-type diterpenes but differ in the absolute configurations at C-7, C-11, and C-14, as well as in the oxidation levels at C-6 and C-8, which were determined through extensive spectroscopic data interpretation. Stereochemical assignments of compounds 1, 2, and 4–12 were established by single-crystal X-ray diffraction, and the absolute configuration of 3 was determined by analysis of the NOESY data and biogenetic consideration. Compounds 2 and 3 were immunosuppressive against lipopolysaccharide (LPS)-induced B cells, with IC50 values of 3.0 and 7.9 μM, respectively. They also moderately suppressed concanavalin A (ConA)-induced T cell proliferation, with IC50 values of 19 and 20 μM, respectively.本研究从真菌卡门青霉（Penicillium camemberti）JSB-7212中分离得到12个高氧化态新型二萜类化合物Penicamins A–L（1–12）。该系列化合物均与缬柏烷（valparane）型二萜共享7/6/5三环骨架，但在C-7、C-11、C-14位的绝对构型以及C-6、C-8位的氧化程度上存在差异，上述结构特征通过大量波谱数据解析得以确证。化合物1、2及4–12的立体化学构型通过单晶X射线衍射确定，而化合物3的绝对构型则通过NOESY谱数据分析结合生源合成推论得以解析。化合物2和3对脂多糖（lipopolysaccharide, LPS）诱导的B细胞增殖具有免疫抑制活性，半数抑制浓度（IC50）分别为3.0 μM和7.9 μM；同时二者还能中度抑制刀豆蛋白A（concanavalin A, ConA）诱导的T细胞增殖，对应的IC50值分别为19 μM和20 μM。