【作者】 李巍；

【导师】 尹建元；

【作者基本信息】 吉林大学 ， 药物化学， 2012， 硕士

【摘要】 西洋参（Panax quinquefolium L.）系五加科（Araliaceae）人参属（Panax）多年生草本植物，原产于美国和加拿大。西洋参又称花旗参、洋参、美国人参和广东参，具有补气养阴、清热生津之功效。西洋参的主要药理活性成分为人参皂苷，具有三萜类结构。按其皂苷元结构可分为三种类型：达玛烷型（Dammarane type）皂苷、齐墩果酸型（Oleanic acid type）皂苷和奥克梯隆型（Ocotillol type）皂苷。人参皂苷具有广泛的医药保健作用，目前它的全合成尚未成功，主要从西洋参、人参中提取分离得到。大量实验研究显示人参皂苷具有调节中枢神经系统、延缓衰老、提高机体免疫力、抗疲劳、改善心脑血管供血不足、抑制肿瘤细胞生长等作用。人参皂苷在体内的代谢研究表明，经过体内水解反应人参皂苷最终代谢生成低极性、便于吸收、生物活性更强的次级皂苷和苷元。但是这些低极性、易于吸收、生物活性更强的次级皂苷和苷元在人参属植物中含量却很少，单纯的依靠提取分离很难从人参属植物中得到大量可供工业化生产用的原料，不利于药品及保健食品的开发利用。因此研究如何从人参属植物中获得极性低、稀有且生物药理活性较好的次级单体皂苷或苷元具有重要的现实意义。目前科研工作者获得次级皂苷或苷元的方法主要有酸降解法、酶降解法、Smith降解法、碱降解法、微生物降解法等方法。本实验室前期研究工作表明，西洋参茎叶皂苷酸降解产物比西洋参茎叶总皂苷具有更强的抗肿瘤活性作用。本文从人参皂苷的分类、人参皂苷的转化途径以及其生物药理活性等方面综述了近年来国内外科研工作者对人参皂苷的研究概况，在总结前人的研究基础上，本课题组首次以西洋参茎叶皂苷为原料，通过对其酸降解制得稀有但有很好药理活性的次级皂苷或苷元，并通过正相柱层析、反相柱层析、制备高效液相法和重结晶对酸降解产物进行分离、纯化得到10个化合物。根据各化合物物理化学性质和光谱解析鉴定了它们的结构，分别为：20(R)-人参二醇（1）、20(R)-人参三醇（2）、达玛-(E)-20(22)-烯-3β,12β,25-三醇（3）、20(R)-达玛-25-乙氧基-3β,12β,20-三醇（4）、(20R,24R)-达玛-20(24)-环氧-3β,12β,25-三醇（5）、达玛-22,23,24,25,26,27-去六碳-20-酮-3β,6α,12β-三醇（6）、20(R)-达玛烷-3β,6α,12β,20,25-五醇（7）、20(S)-达玛烷-3β,6α,12β,20,25-五醇（8）、(20R,24R)-达玛-20(24)-环氧-3β,12β,25-三醇（9）、6-O-β-D-吡喃葡萄糖基-达玛-20(R)-3β,6α,12β,20,25-五醇（10），其中化合物6为首次从西洋参茎叶酸降解产物中分离得到。更多还原

【Abstract】 Panax quinquefolium L., belonging to the genus of panax, araliaceae, and it is nativeto America and Canada. The another name of Panax quinquefolium L. is AmericanGinseng, which was depicted as having many pharmacological functions such asrestorative, tonic, nootropic, antiaging and so on. The pharmacologically activeconstituents of Panax quinquefolium L. are a group of dammarane-type triterpenesaponins known as ginsenosides. The most abundant ginsenosides can be subdividedinto three classes on the basis of the aglycons, dammarane type ginsenosides, oleanicacid type ginsenosides and Ocotillol type ginsenosides. It is well known thatginsenosides have significant effect in a wide range of pathological conditions andhealthcare. Up to now, it is not successful to achieve complete synthesis of ginsenosides,and it need to extract and separate from Panax ginseng or Panax quinquefolium L. tomeet the medical needs. Numerous studies demonstrate that ginsenosides have a broadrange of beneficial effects including regulating central nervous system, anti-aging,promoting the immunity of the organism, antifatigue, meliorating pathology conditionsof cardiovascular system, and inhibiting the growth of tumors and so on. Currentscientific studies have demonstrated that most ginsenosides are metabolized in vivothrough a series of deglycosylation steps into some saponins and aglycon derivativeswith stronger efficacy and easily assimilated. But these saponins and aglycon areextremely low in Panax plants and it is hard to obtain plentiful of saponins or aglyconby isolating from Panax plants, therefore it is not conducive to the development andapplication. Thus the development of saponins and aglycon derivatives with strongerefficacy and easily assimilated has an important theoretical and applied significance.There are several methods to achieve saponins and aglycon in scientific studies, acidhydrolysis, biotransformation, alkaline hydrolysis, Smith hydrolysis and enzyme hydrolysis. Based on previous research of our laboratory, the ginsenosides-hydrolysateexhibited stronger antitumor activity than total ginsenosides.In the thesis, there is a summary of the chemical constituents, hydrolysis methods,bioactivity of ginsinosides about the scientific studies of Panax. On the basis oftheoretical and experimental reports, the chemical constituents of acid degradationproducts of the ginsenosides from the Leaves and stems of Panax quinquefolium L.were studied in this project.10kinds of compounds were isolated and purified from theacid degradation products, using the chromatography such as, column chromatographyof silica gel, reversed phase silica column, semi-preparative high performance liquidchromatography and recrystallization. The chemical structures of10compounds wereelucidated by their physicochemical properties and spectrum analysis. They are,20(R)-panaxadiol (1),20(R)-panaxatriol (2), dammar-(E)-20(22)-ene-3β,12β,25-triol(3),20(R)-dammar-25-ethoxyl-3β,12β,20-triol(4),20(R),24(R)-dammar-20(24)-epoxy-3β,1β,25-triol(5),3β,6α,12β-triol-22,23,24,25,26,27-hexanordammaran-20-one(6),20(R)-dammar-3β,6α,12β,20,25-pentol(7),20(S)-dammar-3β,6α,12β,20,25-pentol(8),20(S),24(R)-dammar-20(24)-epoxy-3β,6α,12β,25-tetraol(9),6-O-β-D-glucopyranoside-dammar-20(R)-3β,6α,12β,20,25-pentol(10). Compound6was separated from the aciddegradation products of the ginsenosides from the Leaves and stems of Panaxquinquefolium L. for the first time.更多还原