【作者】 邢瑞；

【导师】 尹建元；

【作者基本信息】 吉林大学 ， 药物化学， 2009， 硕士

【摘要】 为制备新人参二醇,本论文采用人参根总皂苷为原料,分别用盐酸、硫酸、醋酸的乙醇溶液对人参根总皂苷进行降解。三种酸的乙醇溶液均可降解得到新人参二醇,但以硫酸的转化率最高。以新人参二醇为目标产物,通过正交试验及验证试验,确定了最优降解条件。并建立了HPLC法测定新人参二醇的最佳色谱条件,同时进行了方法学及含量测定的研究。本论文应用计算机模拟技术,计算了新人参二醇、人参皂苷-Rg₃和原人参二醇与目标蛋白的作用程度,结果显示新人参二醇可有效抑制β蛋粉样蛋白的β折叠,为预防及治疗老年痴呆症提供了一定的理论依据。基于分子模拟试验,本文对新人参二醇进行了糖苷化的研究。采用三氯乙酰亚氨酸酯取代端基的葡萄糖作为糖供体,在路易斯酸催化下进行糖苷合成,探索性地进行了方法学考察,TLC显示反应可行。本研究为新人参二醇的制备提供了可靠的实验数据,为其作为抗老年痴呆症的新药研发提供理论指导和技术支持;以新人参二醇作为母核进行各种糖苷反应,为新药研发储备化合物资源。更多还原

【Abstract】 Panax ginseng C.A.Meyer,which is widely used as traditional Chinese medcine,its products are increasingly popular and readily available in pharmacies and health food around the world.Ginsenosides which are the main bioactive components of Panax ginseng,have unique pharmacological activity.In this thesis,the acid degradation process of total ginsenosides in the roots of ginseng,at the same time,the mothed of glycosylation of novel panaxadiol were studied.The sense of this thesis is for the further study of the medicinal value of ginseng,for new drug research reserves compounds basic.1.Literature reviewGinseng as one of the traditional Chinese medicine,it has a long history in our country, ginsenosides were the main effect comoonent,both domestic and foreign scholars were isolated 63 kinds of ginsenosides from ginseng.A large number of studies showed that ginsenosides can suppress tumor cell growing and anti-fatigue,slow aging,improve immunity,improve the cardio- and cerebro-vascular insufficiency and so on.2.Degradation process of total saponins of Panax ginseng rootsIn this paper,we used strong acid（HCl,H₂SO₄） weak acid（HAc） ethanol solution separately degradation total saponins of Panax ginseng root,the target compound was novel panaxadiol.Through single factor test,we chosed acid type,acid concentration,degradation time and degradation temperature four factors for degradation process researching.The results showed that the optimal conditions for degradation was 80℃,7%sulfuric acid degradation 8 h.Application of the above method on degradation,the degradation was stability,and degradation rate was higher.3.The novel panaxadiol’s HPLC researchingWe firstly used HPLC for the content of novel panaxadiol.Chromatographic conditions: Kromasil C₁₈ column（4.6 mm×250 mm,5μm）,mobile phase was methanol - water（90:10）, flow volume was 1.0 mL/min,detection wavelength was 203 nm,column temperature was 35℃,injection volume was 10μL.On the conditions,the results were the linear range of 0.2～4.0μg and correlation coefficient r was 0.9998.The precision test’s RSD was 0.70%,the stability test’s RSD was 1.13%,the reproducibility test’s RSD was 1.85%,recovery test for 0.42%of RSD. 4.Studied on the novel panaxadiol with amyloidβmolecular simulationIn this paper,we innovatively used molecular docking approach,the target was amyloid 13 protein,taken the novel panaxadiol,protopanoxadiol and ginsenoside-Rg₃ as small molecule probes,carried out the molecular simu- lation,in order to put forward a new theory and the possible mechanism of interaction between the two models,the novel panaxadiol and amyloidβprotein,as.well as provided orientation of further study.In this study,two innovative mechanism of drugs were proposed:one mechanism,β-sheet in the horizontal position of the three small molecules,respectively,from the side of amyloidβ,in space there was on steric effects,effectively blockedβ-sheet further formed;mechanism two,β-sheet in the vertical position,separately for the three small molecule amyloidβprotein from one side, constitute a steric inter-layer.The results showed that the horizonta binding energy of novel panaxadiol with amyloidβwas -4.59 kal/mol 1,vertical integration to -6.19 kal/mol.At the same time,the novel panaxadiol’s 3-OH part in the internalβ-sheet,modified the 3-OH was the method of stabilization of the novel panaxadiol and amyloidβ.This had the important role on the treating and preventing AD.5.The glycosilation of novel panaxadiolThrough molecular modeling studies,we could conclud that the novel panaxadiol’s 3-OH was the role of the target,taken glycosilation can be combined with the protein more stable conducive to prevent theβ-sheet,so as to effectively prevent and treat AD.In this test purpose,the glycosilation of the novel panaxadiol test was studied.The suger donator was 2,3,4,6 - tetra- O- ac etyl-β-D-gluxosyl-trichloroacetic ester imide.The suger acceptor was the novel panaxadiol.,and catalytic agent was TMSOTf.Through the analysis,we coule simply arrive at the novel panaxadiol connected with glucose,but the exact location of the connection had to be further studied.6.The innovative and value of researchingThe novel panaxadiol was new compounds in ginseng root,one of the sapogenins.Acid degradation process and HPLC studies were the firstly.In addition,this article innovatively took technologies in molecular simulation on ginseng,and predicted two mechanisms of novel panaxadiol with amyloidβprotein.Glycosilation of novel panaxadiol was under the molecular simulation guidance.All the results of the study can offer credible foundation for the development of new anti-Alzheimer’s disease.更多还原