去甲斑蝥素磷酸二钠盐衍生物的设计与合成

去甲斑蝥素磷酸二钠盐衍生物的设计与合成

周玥, 蔡于琛, 张学景, 王志新, 冼励坚, 邹永*

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

收稿日期:2005-12-20 修回日期:2006-02-10 出版日期:2006-03-15 发布日期:2006-03-15
通讯作者: 邹永*

Design and Synthesis of Disodium Phosphate Derivatives of Norcantharidin

ZHOU Yue, CAI Yu-chen, ZHANG Xue-jing, WANG Zhi-xin, XIAN Li-jian, ZOU Yong*

1.Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650, China;
2.Cancer Center of Zhongshan University, Guangzhou 510060, China

Received:2005-12-20 Revised:2006-02-10 Online:2006-03-15 Published:2006-03-15
Contact: ZOU Yong*

摘要/Abstract

摘要： 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: 去甲斑蝥素, 去甲斑蝥素, 去甲斑蝥素, 磷酸二钠盐, 磷酸二钠盐, 磷酸二钠盐, 设计, 设计, 设计, 合成, 合成, 合成

Abstract: Aim To design and synthesize norcantharidin disodium phosphate derivatives. Methods Diels-Alder reaction between furan and maleic anhydride afforded dehydronorcantharidin, and subsequent hydrogenation, phosphorylation, and basification gave compounds 1 and 2, separately. Results 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 MGC803 cell lines. Conclusion The phosphorylation of norcantharidin analogues is an effective way to increase the activity and solubility.

Key words: norcantharidin, norcantharidin, disodium phosphate, disodium phosphate, design, design, synthesis, synthesis

中图分类号:

R916.4

R916.696

Supporting: Foundation item: Natural Science Foundation of Guangdong Province (040022461) ; Science and Technology Program of Guangdong Province (2003B31603).
^*Corresponding author. Tel.: 86-20-85231309; fax: 86-20-85231119

周玥, 蔡于琛, 张学景, 王志新, 冼励坚, 邹永*. 去甲斑蝥素磷酸二钠盐衍生物的设计与合成[J]. .

ZHOU Yue, CAI Yu-chen, ZHANG Xue-jing, WANG Zhi-xin, XIAN Li-jian, ZOU Yong*. Design and Synthesis of Disodium Phosphate Derivatives of Norcantharidin[J]. .

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