Improved synthesis and characterization of L-histidine norcantharimide,a novel potent protein phosphatase 2A inhibitor  

新型蛋白磷酸酶抑制剂L-组氨酸去甲斑蝥酰亚胺的高效合成及其表征(英文)

作　　者：陈大峰[1] 邹永[1] 李永强[2] 蔡于琛[2] 冼励坚[2] 

机构地区：[1]中国科学院广州化学研究所,广东广州510650 [2]华南肿瘤生物学国家重点实验室

出　　处：《Journal of Chinese Pharmaceutical Sciences》2008年第2期134-137,共4页中国药学（英文版）

基　　金：Science and Technology Program of Guangdong Province(Grant No.2006B35604002);Guangzhou City(Grant No.2007JI-C0261).

摘　　要：Improved synthesis and structure identification of L-histidine norcantharimide , a potent PP2A inhibitor was reported. Condensation between norcantharidin and L-histidine in 95% EtOH at reflux temperature affords L-histidine norcantharimide in 97.0f% yield which is much higher compared with literature, and more importantly, the configuration is retained. The chemical structure of the compound was re-elucidated through IR, FAB-MS, ^1H NMR, ^13C NMR and 2D NMR （^1H, ^13C-COSY and HMBC）, the fundamental physical data, including optical data being also firstly reported. Preliminary cytotoxicity evaluation showed that the target compound was probably more potent than norcantharidin against a panel of human cancer cell lines. Design and synthesis of amino acid （nor） cantharirnides would provide a convenient and rational structure modification of （nor） cantharidin and open new avenues to explore new promising candidates.报道一种新型蛋白磷酸酶抑制剂的高效合成方法及其结构表征。L-组氨酸和去甲斑蝥素在95%乙醇中回流,缩合生成L-组氨酸去甲斑蝥酰亚胺。该反应收率为97.0%,远远高于文献值。更重要的是,缩合产物保持了L-立体构型。利用IR,FAB-MS,~1H NMR,^(13)C NMR和2D NMR(~1H,^(13)C-COSY和HMBC)等对缩合产物进行了结构表征;此外,还首次报道了包括其旋光度在内的物理常数数据。初步的细胞毒性评价表明,与去甲斑蝥素相比,目标化合物在生长抑制活性试验中对一些人体癌细胞株显示了更好的抑制活性。氨基酸去甲斑蝥酰亚胺的设计与合成为(去甲)斑蝥素衍生物结构改造提供了新思路。

关 键 词：Norcantharmide NORCANTHARIDIN L-HISTIDINE 

分 类 号：R914[医药卫生—药物化学]