湖北栝楼种子、驳骨丹和鱼腥草化学成分研究

【作者】 郗砚彬；

【导师】 巢志茂；

【作者基本信息】 中国中医科学院 ， 中药学， 2007， 硕士

【摘要】 本论文共分为三部分，第一部分为驳骨丹化学成分研究，第二部分为湖北栝楼种子不皂化部分化学成分研究，第三部分为鱼腥草化学成分研究。第一部分驳骨丹化学成分研究驳骨丹(Gendarussa vulgaris Nees.)为爵床科(Acanthaceae)驳骨草属(Gendarussa)植物，以茎、叶入药，味辛、苦，性平，归肝、肾、肺经。生于丘陵草坡，路旁村边或灌丛中。分布于台湾、广东、海南、广西、云南等地。具有祛风湿，散淤血，续筋骨的功效，主治风湿痹痛，月经不调，产后腹痛，跌打损伤，骨折。驳骨丹作为一种民族传统用药，有着广泛的临床应用。为了更好的阐明其有效成分和药用机理，作者对驳骨丹(Gendarussa vulgaris Nees.)化学成分进行了研究。本部分共分两章：第一章爵床科植物文献综述查阅了近50年来有关爵床科植物的国内外文献研究资料，对爵床科植物的化学成分和药理作用的研究现状进行了分析和整理，为本课题研究方案的制定和顺利实施提供了有益的借鉴。第二章驳骨丹化学成分研究药材以溶剂提取，通过硅胶柱色谱分离，利用质谱、核磁共振等现代波谱技术鉴定化合物结构。从中共分离并鉴定了5个单体物质，鉴定出3个化合物，分别是：硝酸钾(potassium nitrate，BGD-1)，β-谷甾醇(β-sitosterol，BGD-2)，BGD-3，BGD-4，胡萝卜苷(daucosterol，BGD-5)。BGD-1，BGD-5为首次从驳骨丹中分离。第二部分湖北栝楼种子不皂化部分化学成分研究湖北栝楼(Trichosanthes hupehensis C．Y Cheng et Yueh)系葫芦科(Cucurbitaceae)栝楼属(Trichosanthes L)植物，分布于湖北，湖南，江西，四川，山东，果小瓤绿，皮薄味苦，又名苦瓜蒌。在产地以其果、果皮、种子和根分别作中药瓜蒌、瓜蒌皮、瓜蒌子和天花粉入药。湖北栝楼的根服后有恶心、呕吐现象，属天花粉的混淆品。果实中含有棕榈酸、棕榈油酸、亚麻酸、亚油酸等脂肪酸成分。为了更好的利用药用资源，作者对湖北栝楼种子脂肪油部分进行了提取和皂化，获得不皂化部分，进而对该部分化学成分进行了系统的分离和鉴定。本部分共分两章：第一章葫芦科栝楼属植物文献综述系统地查阅了近30年来有关葫芦科栝楼属植物的国内外文献研究资料，对葫芦科栝楼属植物的化学成分和药理作用的研究现状进行了分析和整理，为本课题研究方案的制定和顺利实施提供了有益的借鉴。第二章湖北栝楼种子不皂化部分化学成分研究作者通过对湖北栝楼种子脂肪油的提取和皂化，获得不皂化部分。该部分经硅胶柱色谱，分离、纯化，并利用质谱、核磁共振等现代波谱技术鉴定了9个化合物。分别是：栝楼仁二醇(karounidiol，HBGL-1)，异栝楼仁二醇(isokarounidiol，HBGL-2)，5-脱氢栝楼仁二醇(5-dehydrokarounidiol，HBGL-3)，7-氧代二氢栝楼仁二醇(7-oxodihydrokarounidiol，HBGL-4)，豆甾-7-烯-3β-醇(stigmast-7-en-3β-ol，HBGL-5)，豆甾-7，22-二烯-3β-醇(stigmast-7，22-dien-3β-ol，HBGL-6)，10α-葫芦二烯醇(10α-cucurbitadienol，HBGL-7)，β-谷甾醇(β-sitosterol，HBGL-8)，豆甾-7，22二烯-3β-O-β-D-葡萄糖苷(stigmast-7，22-dien-3β-O-β-D-glucoside，HBGL-9)。这些化合物为首次从该植物分离获得。第三部分鱼腥草化学成分研究鱼腥草系三白草科(Saururaceae)蕺菜属(Houttuynia Thunb)植物蕺菜(Houttuynia cordata Thunb.)，以新鲜全草或干燥地上部分入药，性辛，味寒，生于丘陵草坡，路旁村边或灌丛中。具清热解毒，消痈排脓，利尿通淋的功能，主要用于肺痈吐脓、痰热喘咳、热痢、热淋、痈肿疮毒。鱼腥草中有效成分属于醛类或甲基酮类，具有抗菌、抗病毒等作用，临床应用广泛。但是，近来发现鱼腥草注射液在临床使用中存在过敏性休克、全身过敏等临床不良反应，为了进一步探明药效物质基础，作者对该类成分进行了研究。第一章鱼腥草中醛类和甲基酮类化学成分及其加成物文献综述系统地查阅了近30年来有关鱼腥草中醛类和甲基酮类化学成分的国内外文献研究资料，对鱼腥草中醛类和甲基酮类化学成分和药理作用的研究现状进行了分析和整理，为本课题研究方案的制定和顺利实施提供了有益的借鉴。第二章鱼腥草化学成分研究亚硫酸氢钠在不需要催化剂的条件下，与醛和某些活泼的酮发生羰基的亲核加成反应，生成稳定的亚硫酸氢钠加成物。这个反应对醛一般可以应用，但酮则要取决于它的结构，特别是烃基的空间位阻。在羰基旁需要有一个甲基，即所谓的甲基酮，才能发生加成反应。反应时用一定浓度的亚硫酸氢钠溶液与醛和甲基酮反应，使平衡尽量的向右进行，产物是一个盐，不溶于乙醚，但溶于水，由于这一反应是一个可逆体系，把存在于体系中的亚硫酸氢钠用酸或碱不断除去，其结果是加成物又分解为原来的醛或甲基酮。鱼腥草中有效成分主要是癸酰乙醛(鱼腥草素)，甲基正壬酮。癸酰乙醛常温条件下不稳定，容易氧化成甲基正壬酮。作者采用乙醚提取鱼腥草干粉，浓缩提取液。提取液中加入15％的亚硫酸氢钠溶液，生成稳定的亚硫酸氢钠加成物。亚硫酸氢钠溶液经少量乙醚洗涤后，加入同体积的乙醚和过量碳酸氢钠，充分反应。取乙醚层，少量蒸馏水洗涤，浓缩，得乙醚提取物。提取物通过硅胶柱色谱分离，利用质谱鉴定化合物结构。从中分离并鉴定出：methyl nonyl ketone(甲基正壬酮，YXC-1)和decanoyl acetaldehyde(癸酰乙醛，YXC-2)，并经亚硫酸氢钠加成反应得到稳定的加成物sodium houttuyfonate(鱼腥草素钠，YXC-3)。总之，本论文在认真分析和总结文献的基础上，对驳骨丹和湖北栝楼种子不皂化部分进行了系统的化学成分研究，从中分离出14个化合物，其中2个化合物为首次从驳骨丹中分离鉴定，9个化合物为首次从湖北栝楼种子中分离鉴定。同时，采用亚硫酸氢钠萃取法提取鱼腥草中醛类和甲基酮类化合物，从中分离出2个化合物并得到1个加成衍生物，证明了采用亚硫酸氢钠加成反应，能够使脂溶性天然醛类化合物与其他脂溶性杂质达到分离，为天然产物中醛类化合物的提取与分离提供了一条可行的方法。更多还原

【Abstract】 The article is composed of three parts, the first part studied on chemical constituents of the stems and leaves of Gendarussa vulgaris; the second part studied on chemical constituents of unsaponifiable matter from the seeds of Trichosanthes hupehensis; the third part studied on chemical constituents from the leaves of Houttuynia cordata.Part 1: studies on chemical constituents of the stems and leaves of Gendarussa vulgarisBo-Gu-Dan, the stems and leaves of Gendarussa vulgaris Nees. (Acanthaceae), growing in hills and scrub next to the village, mainly distributes in Taiwan, Guangdong, Hainan, Guangxi, Yunnan provinces of China. As a traditional Chinese herb, this plant, possessing the actions in removing beriberoid disease, dissipating blood stasis, os symplecticum, has been used for treatment of rheumatic arthralgia, irregular menstruation, postpartum abdominalgia, wound and cataclasis for many years. For the better of illuminating the active chemnical compositions, a systematical investigation on the chemical components of Gendarussa vulgaris has been performed.This part includes two chapters:Chapter 1: Review on the research progress of Acanthaceae.The correlative researching literature (nearly 40 years) about Acanthaceae plants, including chemical components and pharmacological effects, have been presented and summarized.Chapter 2: Studies on Chemical Constituents.From the 75 % alcoholic extracts of the plant, 5 chemical materials have been isolated by column chromatographies with silica gel. and 3 compounds were identified by NMR, MS spectrum. They are: potassium nitrate (BGD-1) , p-sitosterol(BGD-2) , BGD-3, BGD-4, daucosterol (BGD-5) . Among them, BGD-1, BGD-5 were isolated from the plant for the first time.Part 2: Studies on chemical constituents of unsaponifiable matter from the seeds of Trichosanthes hupehensis. Hu-Bei-Gua-Lou, Trichosanthes hupehensis. (Cucurbitaceae), mainly distributes in Hubei, Hunan, Jiangxi, Sichuan, Shandong provinces of China. The fruits, pericarps, seeds, and roots are respective as fructus trichosanthis, semen trichosanthis, pericarpium trichosanthis, radix trichosanthis in China. The root of Hu-Bei-Gua-Lou is adulterant of radix trichosanthis, because of occurring emesis, nausea. Hexadecanoic acid, palmitoleic acid, linoleic acid, linoleic acid were discovered in the pericarp. For the better use of the Hu-Bei-Gua-Lou, a systematical investigation on the unsaponiflable matter from the seeds of Trichosanthes hupehensis has been performed.This part includes two chapters:Chaper 1: Review on the research progress of seeds of Trichosanthes LThe correlative researching literature (nearly 30 years) about seeds of Trichosanthes hupehensis, including chemical components and pharmacological effects, have been presented and summarized.Chapter 2: Studies on chemical constituents of unsaponifiable matter of seeds of Trichosanthes LThe fatty oil from the seeds of T. hupehensis was extracted with petroleum ether. The saponification was carried out with potassium hydroxide. The unsaponifiable matter was isolated and purified by silica gel column chromatography. 9 compounds were elucidated by means of MS, IR, UV, and H-NMR. They are: karounidiol (HBGL-l),isokarounidiol (HBGL-2) , 5-dehydrokarounidiol (HBGL-3) , 7-oxodihyd-rokarounidiol(HBGL-4) , stigmast-7-en-3β-ol (HBGL-5) , stigmast-7,22-dien-3β-ol (HBGL-6) , 10α-cucurbitadienol (HBGL-7) ,β-sitosterol (HBGL-8) , stigmast-7, 22-dien-3β-O-β-D-glucoside (HBGL-9) . These compounds were isolated from the plant for the first time.Part 3: Studies on chemical constituents from the leaves of Houttuynia cordata.Yu Xin-Cao, the stems and leaves of Houttuynia cordata Thunb (Saururaceae), grows in hills and scrub next to the village. As a traditional Chinese herb, this plant, possessing the actions in heat-clearing, detoxicating, treating boils, apocenosis, inducing diuresis, has been used for treatment of lung anthracoma, pyemesis, dyspnea with cough, dysentery, pyretic stranguria, carbuncle, sore. Aldehyde and methyl ketone constituents, possessing antibiosis, antivirus etc, are effective constituent. Recently, shock anaphylacticus, systemic anaphylaxis were discovered in the clinical application. For reseaching adverse reaction and better use of the Yu-Xin-Cao, a systematical investigation on the Aldehyde and methyl ketone constituents from the leaves of Houttuynia cordata Thunb has been performed.This part includes two chapters:Chaper 1: Review on the research progress of aldehyde and methyl ketone constituents of Houttuynia cordata Thunb.The correlative researching literature (nearly 30 years) about Aldehyde and methyl ketone constituents of Houttuynia cordata Thunb., including chemical components and pharmacological effects, have been presented and summarized.Chapter 2: Studies on aldehyde and methyl ketone constituents of Houttuynia cordata Thunb.Lipid-soluble Aldehyde and methyl ketone constituents are formed into water-soluble sodiumα-hydroxyalkanesulfonate derivatives by the addition reaction of sodium bisulfite, and are separated in sodium bisulfite-diethyl ether-water two-phase solvent systems formed into other lipid-soluble materials by adding hydrochloric acid or sodium bicarbonate.Decanoyl acetaldehyde, methyl nonyl ketone are active constituents of Houttuynia cordata Thunb. The diethyl ether extracts of Houttuynia cordata Thunb, are formed into a-hydroxyalkanesulfonate derivatives by the addition reaction of sodium bisulfite, and are separated by adding sodium bicarbonate formed into other lipid-soluble materials. 3 compounds were elucidated by means of MS. They are: decanoyl acetaldehyde(YXC-3) , sodium houttuyfonate(YXC-2) , methyl nonyl ketone(YXC-1) .To sum up, systematical investigations on the chemical components of Gendarussa vulgaris, Trichosanthes hupehensis and Houttuynia cordata Thunb have been performed, 17 compounds have been isolated. Among them, 11 compounds were isolated from this plant for the first time.更多还原