丹参酮IIA衍生物的合成  

Synthesis of Tanshinone IIA Derivatives

作　　者：姚连琦 秦立玙 李雯 刘德龙[1] YAO Lian-qi1, QIN Li-yu3, LI Wen2, L1U De-long(1 School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China; 2 Shanghai Hutchison Pharmaceuticals, Shanghai, 201401, China; 3 Yu Jie Biotectmology Company（Shanghai）, Shanghai, 200120, China)

机构地区：[1]上海交通大学药学院,上海200240 [2]上海和黄药业有限公司,上海201401 [3]禹捷生物技术(上海)有限公司,上海200120

出　　处：《现代生物医学进展》2018年第2期205-209,共5页Progress in Modern Biomedicine

摘　　要：目的:丹参酮IIA是中药丹参的脂溶性成分,具有抗肿瘤、抗氧化、抗心脑血管疾病等多种生理活性。本文拟对其进行结构改造以获得活性更好的丹参酮IIA衍生物。方法:首先,以丹参酮IIA为原料,通过Vilsmeier反应在其16-位引入醛基,再与醋酸胺进行还原胺化反应,以较高收率得到16-位胺甲基取代的丹参酮IIA衍生物。接着,对其氨基进行修饰,得到10个不同N-取代的丹参酮IIA衍生物。同时考察反应温度、反应溶剂和反应时间等条件对还原胺化反应的影响,确定最佳反应条件。结果:通过1H-NMR、13C-NMR以及LC-MS对所有产物结构进行了确认。还原胺化反应的最佳反应条件为:以1,2-二氯乙烷为溶剂,温度保持40℃,反应时间为2h。结论:反应步骤简单、条件温和、产率较高,是合成16-位取代的丹参酮IIA衍生物的理想方法。Objective： Tanshinone IIA is a lipophilic component of traditional Chinese medicine Salvia miltiorrhiza. It has various physiological activities such as anti-tumor, anti-oxidation, anti-cardiovascular and cerebrovascular diseases. Herein, we report the structure modification of Tanshinone IIA to obtain its derivatives with better activity. Structural modification is necessary due to its low activity. Methods： A Vilsmeier reaction of Tanshinone IIA was developed to provide an intermediate with an aldehyde substituent at its 16-position. A 16-aminomethyl substituted Tanshinone IIA derivative was then obtained in high yield via a reductive amination reaction of the above mentioned intermediate with ammonium acetate. After modification of the amino group, 10 Tanshinone IIA derivatives bearing different N-substituents were obtained. The effect of reaction temperature, solvent, time on the reductive amination reaction was investigated. Results： Structures of all the desired products were confirmed by 1H-NMR, 13C-NMR and LC-MS analysis. The optimal reaction conditions were determined as follows： in 1,2-dichloroethane under 40 ℃ for 2 hours. Conclusions： The method provides a simple, mild and efficient synthesis of Tanshinone IIA derivatives.

关 键 词：丹参酮IIA 衍生物 还原胺化 胺甲基 合成 

分 类 号：R33[医药卫生—人体生理学]