天然产物黄连碱的合成工艺改进  

Synthetic process improvement for natural products coptisine

作　　者：胡慭然[1] 邹宗尧 王燕枝 李学刚[1,2] 

机构地区：[1]西南大学药学院,重庆400715 [2]重庆药物过程与质量控制工程技术研究中心,重庆400715

出　　处：《中国药物化学杂志》2014年第6期455-458,共4页Chinese Journal of Medicinal Chemistry

基　　金：科技部十二五科技支撑计划项目(2011BAI13B02-1);西南大学校地合作基金项目(Sz201302);教育部博士点基金项目(20130182110023);重庆市教委重点项目(KJZH14203)

摘　　要：目的改进天然产物黄连碱的合成工艺。方法以2,3-二羟基苯甲醛为起始原料,经环合、缩合和闭环3步反应得到目标化合物黄连碱。其中,主要针对第二步缩合反应的纯化步骤以及第三步闭环反应的溶剂选择和纯化过程做了有效的改进工作。结果中间体和目标产物结构经1H-NMR、13C-NMR图谱数据确证,总收率可达43.0%,目标化合物经HPLC检测纯度高达98.5%。结论改进后的合成方法反应步骤少、操作简单、条件温和、产物收率及纯度较高,有利于工业化生产。Coptisine is a kind of alkaloids w ith a variety of biological activity,such as,inhibition manoamine oxidase type A,selective inhibition and dual inhibition cell proliferation of vascular smooth muscle,inhibition osteoclast differentiation and function,selective regulation the multidrug resistance protein of vascular smooth muscle cells,antifungal,mucosal protection,myocardial protection and so on,w hich is also one of the main ingredients of Coptis chinensis in Chinese herbal medicines. Because of its natural inadequacy and low yield in past synthesis,this article explores a new synthetic process based on the synthetic route by Chen et al.With 2,3-dihydroxybenzaldehyde as the starting material,the coptisine is synthesized after cyclization,condensation and closed-loop. The important improvements include using methanol for recrystallization instead of column chromatography on silica gel to separate and purify intermediates in the second step,also changing the acidic nature and acid strength of reaction medium and purification operation as to free of regulating p H in the third step. Intermediates and this product are identified by1H-NM R and13C-NM R spectral data. The overall yield of the synthesis of coptisine is up to 43. 0%. The target compound is detected of 98. 5% purity.Through the improved synthetic process,this synthesis of coptisine is of few er reaction steps,simple and quick operation,mild conditions. And this synthetic process improves the yield bestially,obtains high purity product and is in favor of industrial production.

关 键 词：黄连碱 合成 工艺改进 

分 类 号：R284.3[医药卫生—中药学]