CN111961113A - 甘草次酸与甘酪二肽复合物及其制备方法 - Google Patents

甘草次酸与甘酪二肽复合物及其制备方法 Download PDF

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CN111961113A
CN111961113A CN202010456474.2A CN202010456474A CN111961113A CN 111961113 A CN111961113 A CN 111961113A CN 202010456474 A CN202010456474 A CN 202010456474A CN 111961113 A CN111961113 A CN 111961113A
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glycyrrhetinic acid
glycylglycine
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朱海亮
张卿
杨永安
魏元刚
钟慧
左婧
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Nanjing Zhichuang Biotechnology Research Institute Co ltd
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Abstract

本发明公开了一类甘草次酸与甘酪二肽复合物；本发明同时公开了所述甘草次酸与甘酪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甘酪二肽复合物可以具有一定的抗压、抗疲劳、抗感染、抗肿瘤、提高免疫力的功效，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。

Description

甘草次酸与甘酪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甘酪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
研究表明，甘草次酸有一定的防癌和抗癌作用。可抑制原癌细胞的信息传递和基因表达.甘草次酸还具有抗病毒感染的作用，还有研究表明，甘草次酸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。
甘草次酸可使结扎总输胆管的家兔、大鼠的血胆红素降低，尿胆红素排泄增加，此作用较葡萄醛酸内酯或蛋氨酸强。对幽门结扎的大鼠有良好的抗溃疡作用。其治疗指数较高。对于健康人和多种动物，甘草次酸能促进钠、水潴留、排钾增加，呈现去氧皮质酮样作用。
甘草次酸的抗病毒作用也十分显著，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。
甘酪二肽,作为肠外营养药物可用于提高患者细胞免疫功能，有效降低危重患者的感染风险，尤其对严重感染、恶性肿瘤等危重病人的治疗和恢复有重要作用。原料药既可以单独作为药物使用。也可以同其它氨基酸复配，还可开发保健品、抗疲劳药物等。另外甘酪二肽可以做美容品。具有一定的抗压、抗疲劳、抗感染、抗肿瘤、提高免疫力的功效。它与甘草次酸的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
1.一类甘草次酸与甘酪二肽的复合物，它有如下通式：
Figure BDA0002509563550000011
2.该甘草次酸与甘酪二肽的复合物的制备方法如下：
步骤1.常温搅拌下，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25℃下搅拌反应活化0.5h,然后加入甘酪二肽(0.345g,0.5mmol),反应液升至45℃反应24h。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＝8:1),得到目标产物。
具体实施方式
Figure BDA0002509563550000021
常温搅拌下，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25℃下搅拌反应活化0.5h,然后加入甘酪二肽(0.345g,0.5mmol),反应液升至45℃反应24h，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＝8:1),得到目标产物，淡黄色固体，产率38％。Mp:146-148℃1H NMR(600MHz,DMSO-d6)δ12.08(s,1H),9.06-8.90(m,2H)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,4H),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+:690.92(C7H9BrO,[M]+)。

Claims (3)

1.一类甘草次酸与甘酪二肽复合物，其特征在于，它具有如下通式：
Figure FDA0002509563540000011
2.根据权利要求1所述的甘草次酸与甘酪二肽的复合物的制备方法，其特征在于，包括以下步骤：
常温搅拌下，将甘草次酸，EDC·HCl，HOBT，DMAP溶于DMF中，在25℃下搅拌反应活化0.5h,然后加入甘酪二肽，反应液升至45℃反应24h。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，得到目标产物。
3.根据权利要求2所述的制备方法，其特征在于，硅胶柱层析洗脱剂VPE:VAcOEt＝8:1。
CN202010456474.2A 2020-05-26 2020-05-26 甘草次酸与甘酪二肽复合物及其制备方法 Withdrawn CN111961113A (zh)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112245436A (zh) * 2020-11-25 2021-01-22 中国农业大学 18β-甘草次酸在制备增强机体抗疲劳能力的产品中的应用
CN116196248A (zh) * 2023-03-30 2023-06-02 河南大学 一种干细胞修护精华液及其制备方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112245436A (zh) * 2020-11-25 2021-01-22 中国农业大学 18β-甘草次酸在制备增强机体抗疲劳能力的产品中的应用
CN112245436B (zh) * 2020-11-25 2021-08-31 中国农业大学 18β-甘草次酸在制备增强机体抗疲劳能力的产品中的应用
CN116196248A (zh) * 2023-03-30 2023-06-02 河南大学 一种干细胞修护精华液及其制备方法

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