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有机化学 ›› 2012, Vol. 32 ›› Issue (01): 178-182.DOI: 10.6023/cjoc1105102 上一篇    下一篇

研究简报

N-二异丙基磷酰化氨基酸-N-4-氨基吡啶衍生物的合成及对河豚毒素(TTX)解毒生物活性的研究

方华, 陈伟珠, 洪碧红, 张怡评, 易瑞灶   

  1. 国家海洋局第三海洋研究所 海洋生物资源化学与化工中心 厦门 361005
  • 收稿日期:2011-05-10 修回日期:2011-07-25 发布日期:2011-09-15
  • 通讯作者: 方华 E-mail:fhua6115@gmail.com
  • 基金资助:

    国家自然科学基金(No. 40806032)、福建自然科学基金(Nos. 2009J05099, 2010NZ0001-2)资助项目.

Synthesis of N-4-Pyridyl Amide Derivatives of N-Diisopropyloxyphosphoryl Amino Acids and Antidotal Activity of Tetrodotoxin (TTX)

Fang Hua, Chen Weizhu, Hong Bihong, Zhang Yiping, Yi Ruizao   

  1. The Third Institute of Oceanography of the State Oceanic Administration, Xiamen 361005
  • Received:2011-05-10 Revised:2011-07-25 Published:2011-09-15
  • Contact: Fang Hua E-mail:fhua6115@gmail.com
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 40806032), and the Natural Science Foundation of Fujian Province (Nos. 2009J05099, 2010NZ0001-2).

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通过母体化合物4-氨基吡啶(4-AP)与N-二异丙基磷酰化氨基酸(DiPP-AA)在Ph3P 和C2Cl6体系下的缩合反应, 将具有生物活性的氨基吡啶环引入到磷酸化氨基酸结构中, 设计、合成了5 个N-二异丙基磷酰化氨基酸-N-4-氨基吡啶衍生物A1～A5. 所有目标化合物均经IR, 1H NMR, 13C NMR, 31P NMR, MS 的表征. 初步生物活性测试结果表明: 目标化合物对河豚毒素(TTX)中毒的小鼠均有一定的解毒作用, 并不同程度地延长了生存时间, 而且毒性比母体化合物降低了.

关键词: 4-氨基吡啶(4-AP), 河豚毒素(TTX), 质谱裂解, 解毒活性

Some novel 4-aminopyridine derivatives of the title compounds containing the unit of N-diisopropyloxyphosphoryl amino acids were synthesized. Their structures were confirmed by IR, 1H NMR, 13C NMR, and mass spectra. In the present work, a group of 4-aminopyridine derivatives were synthesized in order to find novel structure with higher antagonize effects and lower toxity. On the other hand, their fragmentation behaviors were investigated by positive ion electrospray ionization mass spectrometry in conjunction with tandem mass spectrometry. The preliminary bioassay results showed that chemical modification of 4-aminopyridine possessed stronger bioactivity of antidote tetrodotoxin intoxication.

Key words: 4-aminopyridine (4-AP), tetrodotoxin (TTX), ESI-MS/MS, antidote