新型苦参碱衍生物的水相合成及其晶体结构
收稿日期: 2017-09-13
修回日期: 2017-10-11
网络出版日期: 2017-12-05
基金资助
国家自然科学基金（No.21272144）和中央高校基本科研业务费专项资金（Nos.1301030054，X2015YB06）资助项目.
Synthesis of New Matrine Derivatives in Aqueous Phase and Their Crystal Structures
Received date: 2017-09-13
Revised date: 2017-10-11
Online published: 2017-12-05
Supported by
Project supported by the National Natural Science Foundation of China (No. 21272144) and the Fundamental Research Funds for the Central Universities (Nos. 1301030054, X2015YB06).
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.
王伟, 吕梦娇, 赵利霞, 张娅玲, 李本浩, 李宝林 . 新型苦参碱衍生物的水相合成及其晶体结构[J]. 有机化学, 2018 , 38(4) : 883 -889 . DOI: 10.6023/cjoc201709021
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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