School of Pharmaceutical Science and Technology, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China.
School of Pharmaceutical Science and Technology, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China.
Bioorg Chem. 2019 Apr;85:357-363. doi: 10.1016/j.bioorg.2019.01.013. Epub 2019 Jan 10.
In this paper, the mechanism of orobanone analogues formation via aromatization rearrangement of curcumol was minutely explored. Aromatization of curcumol with acetone under acidic condition was selected as the model reaction. The formation of a stable aromatic system was the driving force for this reaction. Based on the model reaction, other four new orobanone analogues were prepared through curcumol reacting with different carbonyl compounds. The results showed that the stability of carbocation, which was generated from the carbonyl compounds, and the steric hindrance were main factors affecting the aromatization. We also synthesized the analogue of aromaticane B using compound 2. In vitro anti-proliferative activity of some derivatives were tested by MTT assay. Two derivatives showed weak anti-tumor effect on two cancer cell lines (HepG2 and MCF7) under normoxia. Four orobanone analogue 2, 5, 6 and 9 significantly inhibited hypoxia-induced HIF-1 luciferase reporter activity in HeLa cells with the IC values of 13.6, 6.6, 2.4 and 18.2 μM, respectively.
本文详细探讨了莪术醇通过芳构化重排形成莪酮类似物的机理。选择莪术醇与丙酮在酸性条件下的芳构化为模型反应，该反应的驱动力是形成稳定的芳香体系。基于该模型反应，通过莪术醇与不同羰基化合物反应，制备了另外四个新的莪酮类似物。结果表明，羰基化合物生成的碳正离子的稳定性和空间位阻是影响芳构化的主要因素。我们还使用化合物 2 合成了芳香烷 B 的类似物。通过 MTT 法测定了一些衍生物的体外增殖活性。在常氧条件下，两个衍生物对两种癌细胞系（HepG2 和 MCF7）表现出较弱的抗肿瘤作用。四种莪酮类似物 2、5、6 和 9 对 HeLa 细胞中缺氧诱导的 HIF-1 荧光素酶报告基因活性的抑制作用显著，IC 值分别为 13.6、6.6、2.4 和 18.2 μM。
