Synthesis of 9-Substituted Berberine Derivatives with Microwave Irradiation  

作　　者：HAN Xie SHAO Kaiyuan HU Wenxiang 

机构地区：[1]School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430000, P. R. China [2]Jingdong Xianghu Microwave Chemistry Union Laboratory, Beijing Excalibur Space Military Academy of Medical Sciences, Belling 101601, P. R. China [3]Space Systems Division, Strategic' Support Troops, Chinese People's Liberation Army, Beijing 100101, P. R. China

出　　处：《Chemical Research in Chinese Universities》2018年第4期571-577,共7页高等学校化学研究（英文版）

摘　　要：Hyperglycemia is frequently accompanying with hyperlipidemia. To explore the potent drugs with dual-activity and dual-site effects that could reduce blood glucose and blood lipid at the same time, fibrate group with lipid-lowering effect on the 9th position of berberine（BBR） was introduced using the drug design combination principle and the multi-target collaborative treatment method, Moreover, the molecular structure of BBR was modified, and six 9-substituted derivatives of BBR were designed and synthesized, among which, five compotmds have never been reported before. In addition, the molecular structttres of these derivatives were identified using liquid chromato- graphy-mass spectrometry（LC-MS）, IH nuclear n^tgnetic resonance（1H NMR） and 13C NMR, respectively. Fu^her- more, the microwave irradiation experimental technique was applied in the synthesis reaction using the novel micro- wave synthesizer, which accelerated the reaction rate, enhanced the reaction yield, reduced the reaction by-products, and simplified the post-processing steps. In the meantime, the 9-position regioselective demethylation of BBR was explored through quantum chemical calculation during the synthesis of berberrubine. The computations were consistent with the experimental results, which contributed to deducing the mechanism of its selective methylation.Hyperglycemia is frequently accompanying with hyperlipidemia. To explore the potent drugs with dual-activity and dual-site effects that could reduce blood glucose and blood lipid at the same time, fibrate group with lipid-lowering effect on the 9th position of berberine（BBR） was introduced using the drug design combination principle and the multi-target collaborative treatment method, Moreover, the molecular structure of BBR was modified, and six 9-substituted derivatives of BBR were designed and synthesized, among which, five compotmds have never been reported before. In addition, the molecular structttres of these derivatives were identified using liquid chromato- graphy-mass spectrometry（LC-MS）, IH nuclear n^tgnetic resonance（1H NMR） and 13C NMR, respectively. Fu^her- more, the microwave irradiation experimental technique was applied in the synthesis reaction using the novel micro- wave synthesizer, which accelerated the reaction rate, enhanced the reaction yield, reduced the reaction by-products, and simplified the post-processing steps. In the meantime, the 9-position regioselective demethylation of BBR was explored through quantum chemical calculation during the synthesis of berberrubine. The computations were consistent with the experimental results, which contributed to deducing the mechanism of its selective methylation.

关 键 词：Berberine derivative Microwave irradiation Quantum chemistry Regioselectivity 

分 类 号：O636.1[理学—高分子化学] TQ223.121[理学—化学]