Cadinane Sesquiterpenoids and Their Glycosides from <i>Alangium chinense</i> That Inhibit Spontaneous Calcium Oscillations

Nine new cadinane sesquiterpenoids, alanenses A–I (1–9), were isolated from the leaves of Alangium chinense together with three previously reported analogues (10–12). The structures of these molecules were elucidated by interpretation of spectroscopic and spectrometric data. Absolute configurations were established by the comparison of experimental and calculated ECD data, chemical degradation studies for sugar moieties, and a single-crystal X-ray diffraction analysis. Compounds 1 and 2 were isolated as racemates, and enantiopurification was achieved by chiral HPLC. Compounds 3–5 are glycosylated cadinanes bearing a β-d-glucose unit, while compounds 6–9 incorporate a hydroxymethyl group in either the free form or additional ring fusion. The structure of compound 11 was originally misassigned and later revised using additional NMR data. The corrected structure is here supported by X-ray single-crystal analysis. Compounds 1 and 2 inhibit spontaneous calcium channel oscillations at low micromolar concentrations.九个全新的卡达烷型倍半萜（cadinane sesquiterpenoids）类化合物——八角枫素A~I（1~9），从八角枫（Alangium chinense）的叶片中分离得到，同时还分离得到了3个已有报道的类似物（10~12）。通过光谱及波谱数据解析，阐明了所有化合物的平面结构。借助实验电子圆二色谱（electronic circular dichroism, ECD）与计算ECD数据比对、糖基部分的化学降解研究以及单晶X射线衍射分析，确定了各化合物的绝对构型。化合物1和2以消旋体形式被分离，通过手性高效液相色谱（chiral HPLC）实现了对映体纯化。化合物3~5为带有β-D-葡萄糖单元的糖基化卡达烷类化合物，而化合物6~9则在游离形式或额外环融合位点引入了羟甲基。化合物11的结构最初存在错判，后通过补充核磁共振（nuclear magnetic resonance, NMR）数据完成修正，修正后的结构得到了单晶X射线衍射分析的验证。在低微摩尔浓度下，化合物1和2可抑制自发性钙通道振荡。