新型苦参碱衍生物的水相合成及其晶体结构（英文）

Synthesis of New Matrine Derivatives in Aqueous Phase and Their Crystal Structures

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、^(13)C 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.

Thirteen matrine derivatives were synthesized with high yield with one step in aqueous phase. The chemical struc- tures of the synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS. Three crystals of compound 13-（piperidin-l-yl）matrine （a）, 13-（piperidin-l-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）, ll（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（gA）＇＂O（1） by analyzing the data of compound 13-（piperidin-l-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.