Design and Synthesis of Disodium Phosphate Derivatives of Norcantharidin  

去甲斑蝥素磷酸二钠盐衍生物的设计与合成(英文)

作　　者：周玥[1] 蔡于琛[2] 张学景[1] 王志新[1] 冼励坚[2] 邹永[1] 

机构地区：[1]中国科学院广州化学研究所,广东广州510650 [2]中山大学肿瘤防治中心,广东广州510060

出　　处：《Journal of Chinese Pharmaceutical Sciences》2006年第1期28-32,共5页中国药学（英文版）

基　　金：NaturalScienceFoundationofGuangdongProvince(040022461);ScienceandTechnologyProgramofGuangdongProvince(2003B31603)

摘　　要：Aim To design and synthesize norcantharidin disodium phosphate derivatives. Methotis Diels-Alder reaction between furan and maleic anhydride afforded dehydronorcantharidin, and subsequent hydrogenation, phosphorylation, and basification gave compounds 1 and 2, separately. Resuits The structures of compounds were confirmed by IR, NMR and FAB-MS. The aqueous solubility of 1 and 2 were improved, compared with the parent compounds, and their activities were more potent than norcantharidin 4 against MGCS03 cell lines. Conclusion The phosphorylation of norcantharidin analogues is an effective way to increase the activity and solubility.目的设计合成去甲斑蝥素的磷酸二钠盐。方法呋喃和顺丁烯二酸酐经过Diels-Alder制得去甲去氢斑蝥素,再通过一系列的加氢、磷酸化,碱化等反应,制得目标化合物1和2。结果成功合成了去甲斑蝥素磷酸二钠盐,其药理活性以及水溶性较母体化合物有很大提高。结论磷酸化是提高此类药物活性和水溶性的有效手段。

关 键 词：NORCANTHARIDIN disodium phosphate DESIGN SYNTHESIS 

分 类 号：R914[医药卫生—药物化学]