半合成
高三尖杉酯碱
化学
衣康酸
对映选择合成
立体化学
组合化学
白血病
有机化学
催化作用
共聚物
医学
内科学
聚合物
作者
Yujian Yang,Qiuchun Yu,Le’an Hu,Botao Dai,Ruxi Qi,Yu Chang,Qingwen Zhang,Zhang Zhang,Yingjun Li,Xumu Zhang
标识
DOI:10.1016/j.ejmech.2022.114731
摘要
Cephalotaxine-type alkaloids (CTAs), represented by homoharringtonine (HHT, 1), display potent efficacy against different types of leukemia cells. In this study, a method for hydrogenation of β-substituted itaconic acid monoesters with chiral Ru[DTBM-SegPhos](OAc)2 was developed. This metal-catalyzed asymmetric hydrogenation enabled the convenient semisynthesis of novel cephalotaxine derivatives with chiral 2'-substituted-succinic acid 4-mono-methyl esters as side chains. The preliminary structure-activity relationship (SAR) of the compounds' antineoplastic activities was studied. Eventually, we discovered compound 10b with potent antineoplastic activities against leukemia and broadly anticancer activities against a panel of cancer cells. Our study provided a highly enantioselective process enabling the semisynthesis of cephalotaxine derivatives, which are interesting for further study on a scientific basis.
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