鲁宽科, 陈耀祖. 4-S-(5″-烃基-4″-氨基-1″,2″,4″-三唑-3″-基)-4-去氧-4′-去甲基表鬼臼毒素衍生物的合成及抗肿瘤活性J. 药学学报, 1999, 34(1): 63-66.
引用本文: 鲁宽科, 陈耀祖. 4-S-(5″-烃基-4″-氨基-1″,2″,4″-三唑-3″-基)-4-去氧-4′-去甲基表鬼臼毒素衍生物的合成及抗肿瘤活性J. 药学学报, 1999, 34(1): 63-66.
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Lu Kuanke, Chen Yaozu. SYNTHESIS AND ANTITUMOR ACTIVITIES OF 4β-S-(5″-ALKYL-4″-AMINO-1″,2″,4″-TRIAZOLE-3″-YL)-4-DEOXY-4′-O-DEMETHYL-EPIPODOPHYLLOTOXIN DERIVATIVESJ. Acta Pharmaceutica Sinica, 1999, 34(1): 63-66.
Citation: Lu Kuanke, Chen Yaozu. SYNTHESIS AND ANTITUMOR ACTIVITIES OF 4β-S-(5″-ALKYL-4″-AMINO-1″,2″,4″-TRIAZOLE-3″-YL)-4-DEOXY-4′-O-DEMETHYL-EPIPODOPHYLLOTOXIN DERIVATIVESJ. Acta Pharmaceutica Sinica, 1999, 34(1): 63-66.
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4-S-(5″-烃基-4″-氨基-1″,2″,4″-三唑-3″-基)-4-去氧-4′-去甲基表鬼臼毒素衍生物的合成及抗肿瘤活性

SYNTHESIS AND ANTITUMOR ACTIVITIES OF 4β-S-(5″-ALKYL-4″-AMINO-1″,2″,4″-TRIAZOLE-3″-YL)-4-DEOXY-4′-O-DEMETHYL-EPIPODOPHYLLOTOXIN DERIVATIVES

    摘要
  • 摘要: 许多有显著抗肿瘤活性的鬼臼毒素类化合物，其母核C-4侧链上往往连接有刚性较强的脂环或芳香环结构，而且侧链多含有一定数量的杂原子［1～3］。另外，三氮唑类化合物大都有广泛的生物活性，如抗菌［4～5］、抗病毒［6］、抗肿瘤［7］等，据此，我们设计并合成了8个三氮唑杂环取代的表鬼臼毒素衍生物，以期寻找活性高、毒副作用小的鬼臼毒素类药物，并进一步考察此类化合物的构效关系。　合成路线如图1所示，三氮唑3a～3h和4′-去甲基-表鬼臼毒2分别按文献［8，9］方法合成;我们选择三氟乙酸作为缩合剂，基于它不仅能催化缩合反应，而且能保护三唑上的氨基官能团，使其不能充当进攻基团；最后一步缩合反应显然经历了一个SN1历程，4′-去甲基-表鬼臼毒 的C-4位上很容易形成一个苄基型碳正离子，由于C-1位有庞大的芳环，加之，进攻的基团也较大，可以预料，这个反应有很强的立体选择性，使C-4β-构型成为主要产物，事实确实如此，在TLC上几乎看不到C-4α-构型的产物。

     

    Abstract: AIM: In order to search for podophyllotoxin analogue agents with fewer side effects and improved activity, the podophyllotoxin derivatives are to be synthesized. METHODS: Eight 4′-demethyl-podophyllotoxin analogues with 4β-S-triazoles have been synthesized from 4′-demethyl-podophyllotoxin. RESULTS: Eight 4′-demethyl-podophyllotoxin derivatives possessing 4β-S-triazoles have been synthesized and their antitumor activities were screened in vitro against HL-60, BGC-823, BcaP, KB and K562 cells. CONCLUSION: The results indicated that these compounds showed high biological activity only towards K562 cells.

     

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