摘要/Abstract

在水相中，以高收率一步合成了13种苦参碱类似物，并借助¹H NMR、¹³C NMR和HRMS对化合物进行了结构表征.通过X射线单晶衍射分析得到化合物13-（哌啶-1-基）苦参碱（a）、13-（哌啶-1-基）二硫代甲酸苦参碱酯（k）和13-（吗啉-4-基）二硫代甲酸苦参碱酯（m）的精确结构，单晶衍射分析数据显示，三种化合物的结构中都包含5个手性碳原子，其绝对构型分别为5（S），6（S），7（R），11（R），13（S）.化合物a单晶结构中含有三个氢键O（2）-H（21B）…N（2），O（2）-H（21A）…O（1）和C（9）-H（9A）…O（1），这些氢键在单晶的形成过程中起着重要的作用.生物活性测试实验显示，所合成的化合物对抑制人结直肠癌细胞SW480、人非小细胞肺癌细胞A549和人表皮鳞癌细胞A431的增殖有一定作用.在苦参碱13位碳上引入氮或硫原子可以提高化合物的抗肿瘤活性.
关键词: 苦参碱, 衍生物, 合成, 晶体
Thirteen matrine derivatives were synthesized with high yield with one step in aqueous phase. The chemical structures of the synthesized compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. Three crystals of compound 13-(piperidin-1-yl)matrine (a), 13-(piperidin-1-yl)carbodithioate matrine (k) and 13-(morpholin-4-yl) carbodithioate matrine (m) were obtained and X-ray diffraction data showed that their structures included five chiral carbon atoms with the absolute configuration of 5(S), 6(S), 7(R), 11(R) and 13(S). Meanwhile, there were three classical hydrogen bonds:O(2)-H(21B)…N(2), O(2)-H(21A)…O(1) and C(9)-H(9A)…O(1) by analyzing the data of compound 13-(piperidin-1-yl) matrine (a). These strong hydrogen bonds can play a key role in the accumulation of crystals. Biological studies indicated that the synthetic derivatives had some inhibitory effect against SW480, A549 and A431 cells. The introduction of N or S atom at C-13 position of matrine could improve the antitumor activity.
Key words: matrine, derivative, synthesis, crystal


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