Cajanusoids A-D, Unusual Atropisomeric Stilbene Dimers with PTP1B Inhibitory Activities from the Leaves of Cajanus cajan
Cajanusoids A-D, Unusual Atropisomeric Stilbene Dimers with PTP1B Inhibitory Activities from the Leaves of Cajanus cajan
复制标题
Cajanusoids A-D，来自木豆叶的具有 PTP1B 抑制活性的不寻常阻转异构二苯乙烯二聚体
DOI：
10.1021/acs.joc.1c00295
复制
发表时间：
2021
影响因子：
3.6
通讯作者：
Wang Ying
中科院分区：
文献类型：
--
作者：
He Qi-Fang;Wu Zhen-Long;Huang Xiao-Jun;Xia Tian-Qi;Tang Genyun;Tang Wei;Shi Lei;Ye Wen-Cai;Wang Ying
从木豆叶片中分离得到四个新的二苯乙烯二聚体(1-4)及其生物合成相关的二苯乙烯单体(5和6)。通过对光谱数据的综合分析和电子圆二色谱计算，确定了它们的绝对构型。化合物1和2是两个新的二聚二苯乙烯，它们具有不寻常的耦合模式，导致了罕见的构型稳定的Csp2-Csp3手性轴，它们的分子中既有点手性又有轴向手性。由于它们独特的固有结构特征，它们都自然地以不均匀填充的阿托波-非对映异构体及其各自的对映体的平衡混合物的形式出现。化合物3和4是两对新型二聚二苯乙烯阿托品，具有旋转受阻的中心联芳轴。值得注意的是，3含有稀有的芳基对苯二酚核，4是具有C2对称轴的对称二聚体。本文还提出了1-4的假想生物合成途径。所有新化合物都有明显的蛋白酪氨酸磷酸酶-1B(PTP1B)抑制作用。此外，通过分子对接和结合自由能计算，初步探讨了最有效的化合物3的作用方式。
Four novel stilbene dimers (1–4), together with their biosynthetically related stilbene monomers (5and6), were isolated from the leaves ofCajanus cajan. Their structures with absolute configurations were determined by comprehensive analysis of spectroscopic data and electronic circular dichroism calculations. Compounds1and2are two novel dimeric stilbenes with an unusual coupling pattern that resulted in a rare configurationally stable Csp2–Csp3chiral axis with both point and axial chirality in their molecules. Due to their unique inherent structural features, both of them naturally occur as equilibrating mixtures of unequally populated atropo-diastereomers and their respective enantiomers. Compounds3and4are two pairs of novel dimeric stilbene atropisomers featuring a rotationally hindered central biaryl axis. Notably,3contains a rare arylbenzoquinone core and4is a symmetric dimer with aC2symmetry axis. The hypothetical biosynthetic pathway of1–4was also proposed herein. All the new compounds exhibited significant protein tyrosine phosphatase-1B (PTP1B) inhibition effects. In addition, the preliminary mode of action for the most potent compound3was investigated by molecular docking and binding free energy calculation.