Shang Zhi-Chun, Yang Ming-Hua, Jian Kai-Li, Wang Xiao-Bing, Kong Ling-Yi
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, P. R. China.
Chemistry. 2016 Aug 8;22(33):11778-84. doi: 10.1002/chem.201601732. Epub 2016 Jul 14.
Nine formyl-phloroglucinolmeroterpenoids (FPMs), namely, eucalrobusones A-I (1-9), were isolated from the leaves of Eucalyptus robusta by tracking the phenolic hydroxyl (1) H NMR peaks. The Snatzke helicity rules for the Cotton effects of twisted benzene rings were applied to elucidate the absolute configurations of the FPMs. These findings, along with NMR spectroscopy, the circular dichroism (CD) exciton chirality method, and CD calculations, allowed complete structures for the FPMs to be assigned. Eucalrobusones A-F (1-6) are novel adducts formed between a formyl-derived carbon atom on the phloroglucinol ring and monoterpene and sesquiterpene components. Eucalrobusones G-I (7-9) are the first examples of FPMs with cubebane part structures connected by an unusual 1-oxaspiro[5.5]undecane subunit. Among these isolates, eucalrobusone C (3) showed significant cytotoxicity against HepG2, MCF-7, and U2OS cancer cell lines, with IC50 values less than 10 μm. Compound 3 significantly blocks cell proliferation in MCF-7 cells and induces MCF-7 cell death through apoptosis.
通过追踪酚羟基的¹H NMR峰，从大叶桉的叶子中分离出九种甲酰基间苯三酚缩聚萜类化合物（FPMs），即桉罗布松A - I（1 - 9）。应用扭曲苯环Cotton效应的Snatzke螺旋规则来阐明FPMs的绝对构型。这些发现，连同核磁共振光谱、圆二色性（CD）激子手性方法和CD计算，使得能够确定FPMs的完整结构。桉罗布松A - F（1 - 6）是间苯三酚环上甲酰基衍生的碳原子与单萜和倍半萜成分之间形成的新型加合物。桉罗布松G - I（7 - 9）是首例具有通过不寻常的1 - 氧杂螺[5.5]十一烷亚基连接的荜澄茄烷部分结构的FPMs。在这些分离物中，桉罗布松C（3）对HepG2、MCF - 7和U2OS癌细胞系显示出显著的细胞毒性，IC50值小于10μm。化合物3显著阻断MCF - 7细胞的增殖，并通过凋亡诱导MCF - 7细胞死亡。
