CN111925410A - 甘草次酸与丙谷二肽复合物及其制备方法 - Google Patents

甘草次酸与丙谷二肽复合物及其制备方法 Download PDF

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CN111925410A
CN111925410A CN202010457705.1A CN202010457705A CN111925410A CN 111925410 A CN111925410 A CN 111925410A CN 202010457705 A CN202010457705 A CN 202010457705A CN 111925410 A CN111925410 A CN 111925410A
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朱海亮
张卿
杨永安
魏元刚
钟慧
左婧
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Abstract

本发明公开了一类甘草次酸与丙谷二肽的复合物；本发明同时公开了所述甘草次酸与丙谷二肽的复合物的制备方法。本发明还公开了所述甘草次酸与丙谷二肽的复合物可以很好的缓解甘草次酸的水溶性，又可以产生很好的药用价值。

Description

甘草次酸与丙谷二肽复合物及其制备方法
技术领域
本发明涉及甘草次酸与丙谷二肽复合物及其制备方法，属于新化合物的提出、制备技术领域。
背景技术
甘草次酸是由甘草酸水解脱去糖酸链而形成的。近年的研究表明，甘草酸和甘草次酸均有一定的防癌和抗癌作用。甘草次酸可抑制原癌细胞的信息传递和基因表达.甘草酸对多种致癌物诱导的试验动物恶性肿瘤菌有抑制作用。甘草次酸还具有抗病毒感染的作用，对致癌性的病毒如肝炎病毒，EB病毒及艾滋病毒的感染均有抑制作用。
甘草次酸还具有保泰松或氢化可的松样的抗炎作用。研究表明，甘草次酸对大白鼠的棉球肉芽肿及甲醛性脚肿、皮下肉芽肿性炎症等均有抑制作用，其抗炎效价约为可的松或氢化可松的1/10。甘草次酸对角叉菜胶引起的大鼠实验性关节炎有抑制作用，对马血清或鸡蛋白所致豚鼠过敏反应均有不同程度的抑制作用。
甘草次酸对多种急性炎症均有抑制作用，其抗炎作用不依赖于垂体一肾上腺皮质系统，而和抑制炎症组织中PgE2生成、拮抗炎症介质组胺、5羟色胺等的作用有关。
甘草次酸还具有一定的抗病毒作用，在体外能增强小檗碱抑制金黄色葡萄球菌的效力，还能中和破伤风毒素的毒力。
丙谷二肽作为氨基酸类肠外营养剂具有很好的药用价值，就像生理盐水、葡萄糖一样，是救护病人的必需品。与甘草次酸形成复合物可以既可以很好的缓解甘草次酸的水溶性，又可以产生很好的药用价值。
发明内容
1.一类甘草次酸与丙谷二肽的复合物，它有如下通式：
Figure BDA0002509898520000011
2.该甘草次酸与丙谷二肽的复合物的制备方法如下：
步骤1.0℃冰水浴搅拌下，将甘草次酸(0.235g,0.5mmol),EDC·HCl(0.12g,0.6mmol),HOBT(0.08g,0.6mmol),DMAP(0.03g,0.25mmol)溶于DMF(10mL)中,在0℃下搅拌反应活化1h,然后加入丙谷二肽(0.109g,0.5mmol),反应液升至45℃反应12h，TCL监测反应进程，反应完全后停止反应,抽滤，收集滤液，用二氯甲烷和水萃取，合并有机相,有机层用无水硫酸钠干燥过夜,硅胶柱层析(洗脱剂VPE:VAcOEt＝4:1)，旋干，烘干得粗产物。
步骤2.将粗产物溶于少量二氯甲烷，爬大板(VPE:VAcOEt＝4:1)。刮下目标产物层，研磨，导入大量二氯甲烷溶液中，旋干，干燥，得纯产物。
具体实施方式
Figure BDA0002509898520000021
0℃冰水浴搅拌下，将甘草次酸(0.235g,0.5mmol),EDC·HCl(0.12g,0.6mmol),HOBT(0.08g,0.6mmol),DMAP(0.03g,0.25mmol)溶于DMF(10mL)中,在0℃下搅拌反应活化1h,然后加入丙谷二肽(0.109g,0.5mmol),反应液升至45℃反应12h，TCL监测反应进程，反应完全后停止反应，抽滤，收集滤液，用二氯甲烷和水萃取，合并有机相,有机层用无水硫酸钠干燥过夜,硅胶柱层析(洗脱剂VPE:VAcOEt＝4:1)，旋干，烘干得粗产物，将粗产物溶于少量二氯甲烷，爬大板(VPE:VAcOEt＝4:1)。刮下目标产物层，研磨，导入大量二氯甲烷溶液中，旋干，干燥，得目标化合物，产率45％。Mp:150-153℃1H NMR(600MHz,DMSO-d6)δ12.06(s,1H),8.90(s,1H),8.76(m,2H),8.32(s,1H),5.50(s,1H),4.55(s,1H),4.32(d,J＝5.1Hz,1H),3.67(s,1H),3.02(dt,J＝11.6,4.8Hz,1H),2.59(dt,J＝13.3,3.6Hz,1H),2.43(t,J＝7.1Hz,2H),2.32(s,1H),2.06–2.07(dt,J＝13.2,6.6Hz,4H),1.94–1.90(m,1H),1.82(dt,J＝13.7,3.5Hz,1H),1.73(dt,J＝13.7,6.9Hz,1H),1.65–1.56(m,2H),1.54–1.48(m,2H),1.43–1.39(m,1H),1.37–1.31(m,5H),1.31–1.22(t,6H),1.13(ddd,J＝13.7,4.8,2.5Hz,1H),1.02(d,J＝11.7Hz,9H),0.95(td,J＝11.6,9.9,3.0Hz,2H),0.91(s,3H),0.72(s,3H),0.71(d,J＝1.9Hz,1H),0.69(s,3H).MS EI+:669.90(C7H9BrO,[M]+)。

Claims (4)

1.一类甘草次酸与丙谷二肽的复合物，其特征在于，它具有如下通式：
Figure FDA0002509898510000011
2.根据权利要求1所述的甘草次酸与丙谷二肽的复合物的制备方法，其特征在于，包括以下步骤：
步骤(1)：0℃冰水浴搅拌下，将甘草次酸，EDC·HCl，HOBT，DMAP溶于DMF中，在0℃下搅拌反应活化1h，然后加入丙谷二肽，反应液升至45℃反应12h，TCL监测反应进程，反应完全后停止反应，抽滤，收集滤液，用二氯甲烷和水萃取，合并有机相,有机层用无水硫酸钠干燥过夜，硅胶柱层析，旋干，烘干得粗产物；
步骤(2)：将粗产物溶于少量二氯甲烷，爬大板。刮下目标产物层，研磨，导入大量二氯甲烷溶液中，旋干，干燥，得纯产物。
3.根据权利要求2所述的制备方法，其特征在于，步骤(1)中，硅胶柱层析洗脱剂VPE:VAcOEt＝4:1。
4.根据权利要求2所述的制备方法，其特征在于，步骤(2)中，爬大板所用材料VPE:VAcOEt＝4:1。
CN202010457705.1A 2020-05-26 2020-05-26 甘草次酸与丙谷二肽复合物及其制备方法 Withdrawn CN111925410A (zh)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113209270A (zh) * 2021-05-17 2021-08-06 宁波大学 丙谷二肽在制备防治急性肝衰竭药物中的应用
CN113332416A (zh) * 2021-05-17 2021-09-03 宁波大学 丙谷二肽在制备治疗非酒精性脂肪肝药物中的应用

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113209270A (zh) * 2021-05-17 2021-08-06 宁波大学 丙谷二肽在制备防治急性肝衰竭药物中的应用
CN113332416A (zh) * 2021-05-17 2021-09-03 宁波大学 丙谷二肽在制备治疗非酒精性脂肪肝药物中的应用
CN113209270B (zh) * 2021-05-17 2022-02-22 宁波大学 丙谷二肽在制备防治急性肝衰竭药物中的应用
CN113332416B (zh) * 2021-05-17 2022-02-22 宁波大学 丙谷二肽在制备治疗非酒精性脂肪肝药物中的应用

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