Cytotoxic Cleistanthane and Cassane Diterpenoids from the Entomogenous Fungus Paraconiothyrium hawaiiense

Hawaiinolides A–D (1–4), four new secondary metabolites including three cleistanthane (1, 3, and 4) and one cassane (2) type of diterpene lactones, were isolated from the crude extract of Paraconiothyrium hawaiiense, a fungus entomogenous to the Septobasidium-infected insect Diaspidiotus sp. The structures of 1–4 were elucidated by nuclear magnetic resonance experiments, and 1 and 3 were further confirmed by X-ray crystallography. The absolute configuration of 1 was assigned via single-crystal X-ray diffraction analysis using Cu Kα radiation, whereas that of 2–4 was deduced via the circular dichroism data. Compound 1 showed significant cytotoxicity against a small panel of five human tumor cell lines, A549, T24, HeLa, HCT116, and MCF-7.从寄生于被隔担耳菌属（Septobasidium）侵染的盾蚧属（Diaspidiotus sp.）昆虫的虫生真菌夏威夷副细盾霉（Paraconiothyrium hawaiiense）的粗提取物中，分离得到4个新的次生代谢产物——夏威夷内酯A–D（1–4），其中包括3个克林斯坦烷（cleistanthane）型二萜内酯（diterpene lactones，化合物1、3和4）与1个卡桑烷（cassane）型二萜内酯（diterpene lactones，化合物2）。通过核磁共振波谱（nuclear magnetic resonance）实验解析了化合物1–4的结构，其中化合物1和3的结构进一步通过X射线晶体衍射（X-ray crystallography）得到确证。化合物1的绝对构型通过采用Cu Kα辐射的单晶X射线衍射分析得以确定，而化合物2–4的绝对构型则通过圆二色谱（circular dichroism）数据推导得出。化合物1对由A549、T24、HeLa、HCT116及MCF-7共5株人肿瘤细胞系组成的小型测试组显示出显著的细胞毒性。