两种药用植物成分及结构多样性吲哚生物碱的制备研究

发布时间：2018-01-04 07:18

本文关键词：两种药用植物成分及结构多样性吲哚生物碱的制备研究　出处：《云南大学》2016年博士论文　论文类型：学位论文

【摘要】：本论文由五章组成。第一章对大戟科(Euphorbiaceae)巴豆属卵叶巴豆(Croton caudatus)的枝叶进行了化学成分研究,并对其得到的部分单体化合物进行了抗肿瘤、抗菌及抗HIV活性研究,从而发现了4个活性化合物。第二章对夹竹桃科(Apocynaceae)鸡骨常山属糖胶树(A. scholaris)的虫瘿叶子进行了生物碱成分研究,并对其得到的新骨架化合物进行了促进神经干细胞增殖的生物活性研究。第三章对糖胶树的根进行了化学成分研究,从中分离鉴定了14个已知化合物。第四章对糖胶树的枝条进行了化学成分研究,从中分离鉴定了11个已知化合物。第五章对多样性吲哚生物碱的制备进行了研究,并对其得到的单体化合物进行了促进胞内钙流活性和促进PC12细胞分化的活性研究,发现了4个活性化合物。运用多种色谱技术(例如：正相硅胶柱色谱、反相硅胶柱色谱、薄层色谱、sephadax LH-20凝胶柱色谱、中压制备色谱、液相超高压制备色谱)和波谱学方法(1D NMR、2D NMR、MS、UV、IR、CD、X-ray单晶衍射和量子化学计算)从上述3种研究对象中共分离鉴定化合物82个,其中24个为新化合物。化合物类型涉及二萜、四萜、大柱香波龙烷苷、黄酮、木脂素、吲哚生物碱等。1、大戟科植物卵叶巴豆的化学成分和生物活性研究卵叶巴豆(Croton caudatus),大戟科巴豆属植物,攀援灌木,其叶卵圆形,故名卵叶巴豆。该植物产于云南西南部,生于海拔500-600米疏林中。分布于印度、斯里兰卡、中南半岛及马来西亚。该属植物以二萜成分为主,而这些二萜成分不仅提供了大戟科植物的化学分类依据,而且也是主要的活性物质。我们对采自云南西双版纳的卵叶巴豆枝叶进行了化学成分研究。从中分离得到了11个化合物,其中有4个二萜、1个大柱香波龙烷苷、3个黄酮、2个木脂素和1个四萜。新化合物4个,包括3个新的tigliane骨架类型二萜和1个新的大柱香波龙烷苷。对3个新的tigliane骨架类型二萜进行了人体肿瘤细胞毒活性实验,发现了化合物1-3均有一定的体外肿瘤抑制活性。对化合物4进行了抗菌和抗HIV活性测试,发现其具有一定的抗菌及抗HIV活性。2、夹竹桃科植物糖胶树虫瘿叶子的化学成分和生物活性研究糖胶树(Alstonia scholaris),夹竹桃科鸡骨常山属植物,木材的材质松软细致,全株乳汁丰富,可提取口香糖原料,故名“糖胶树”。糖胶树叶子俗称“灯台叶”,傣药中用于治疗百日咳、慢性支气管炎等。现在市场上也有云南大唐汉方制药有限公司生产的灯台叶片及昆明振华制药厂有限公司生产的灯台叶颗粒等非处方药用产品。由本课题组研发的五类新药灯台叶总生物碱胶囊具有止咳、平喘、抗炎及镇痛疗效,目前已完成一期临床的相关实验。作为药材研究的一部分,我们对虫瘿的灯台叶进行了化学成分研究,从中共分离鉴定21个单体化合物,包括1个新骨架降C-5吲哚生物碱、19个单萜吲哚生物碱和1个木脂素。3、夹竹桃科植物糖胶树根的化学成分研究我们经过对糖胶树根提取物的研究发现,其液相指纹图谱与叶子的指纹图谱不尽相同,而且糖胶树中已发现的化合物结构骨架种类较多、活性突出,带着发现新结构与活性物质的兴趣与目标,我们对糖胶树根进行了化学成分研究,共分离鉴定14个单体化合物。4、夹竹桃科植物糖胶树枝条的化学成分研究糖胶树树皮记载有治头痛、伤风、痧气、肺炎、百日咳、慢性支气管炎等疗效；外用可治外伤止血、接骨、消肿、疮节及配制杀虫剂等。前期,我们对糖胶树虫瘿叶子、糖胶树根进行了化学成分研究,发现了较多骨架类型的生物碱。本章我们研究了糖胶树枝条的化学成分,期望能够丰富糖胶树中发现的生物碱的化合物库。经过系统的化学成分研究,共分离鉴定了11个单体化合物。5、结构多样性吲哚生物碱的制备及生物活性研究自然界中的单萜吲哚生物碱骨架千变万化,数量较多,但是它们基本都从异胡豆苷衍变而来。而异胡豆苷这个重排单萜吲哚生物碱则由色胺和裂化马钱子苷以1：1的摩尔比在异胡豆苷合成酶的作用下发生Mannich反应得来。然而,我们课题组在对盆架树化学成分的研究过程中发现了色胺和裂环马钱子苷以1：2摩尔比缩合的产物alstrostines A和B,这促使我们思考吲哚生物碱的生源合成途径的多样性。本章以色胺和獐牙菜苦苷为反应底物,制备结构多样的吲哚生物碱,并探究吲哚生物碱的合成途径,共分离鉴定24个化合物,包括23个吲哚生物碱,其中19个为新化合物。对部分吲哚生物碱进行了促进PC12细胞分化和促进胞内钙流活性研究,并从中发现了4个具有促进胞内钙流活性的化合物。
[Abstract]:This thesis consists of five chapters. The first chapter of the Euphorbiaceae Croton leaf egg (Euphorbiaceae) (Croton caudatus) Croton leaves the studies on the chemical constituents, and some of its compounds obtained antitumor, antibacterial and anti HIV activity to study, found 4 compounds in the second chapter. Apocynaceae (Apocynaceae) chicken bone Changshan alstoniascholaris (A. scholaris) leaves galls were studied and the new alkaloids, the skeleton compounds obtained to promote the study of biological activity of the proliferation of neural stem cells. The third chapter of alstoniascholaris root of the studies on the chemical constituents, from the isolation of 14 the fourth chapter of known compounds. Branches of the chemical constituents of alstoniascholaris research, from the isolation of 11 known compounds. The fifth chapter on the diversity of indole alkaloid preparation were studied, and the obtained The monomer compounds were promoting intracellular calcium current activities and promoting the activity of PC12 cell differentiation, 4 compounds were found. Using various chromatographic techniques (such as silica gel column chromatography, reversed-phase silica gel column chromatography, thin layer chromatography, sephadax LH-20 gel column chromatography, preparative liquid pressing, ultra high pressure system preparation of chromatographic and spectroscopic methods (1D, NMR), 2D, NMR, MS, UV, IR, CD, X-ray diffraction and quantum chemical calculation) from the above 3 kinds of research object the isolation and identification of 82 compounds, including 24 new compounds. Compounds involving two terpenes, four terpenes, Dazhu dragon Wangan shampoo, flavonoids, lignans, indole alkaloid.1, Euphorbiaceae Croton leaf egg studies on chemical constituents and Bioactivities of eggs (Croton caudatus), Croton leaf Euphorbiaceae, climbing shrubs, leaves oval, leaves the eggs. The plant named Croton produced in the southwest of Yunnan, Born in 500-600 meters above sea level in thin forests. Distributed in India, Sri Lanka, Indochina and Malaysia. The genus with two terpenoids, and these two terpenoids not only provides the basis for classification of chemical plants of the family Euphorbiaceae, and is the main active substance. We collected from Yunnan Xishuangbanna egg leaf leaves of Croton Study on the chemical constituents. 11 compounds were isolated from the 4, two terpenes, 1 large dragon Wangan 3 column shampoo, 2 flavonoids, lignans and 1 four terpene. 4 new compounds, including 3 new tigliane framework type two terpene and 1 new high column Wangan. Human dragon shampoo cytotoxicity experiment was carried out on 3 NEW tigliane skeleton type two terpene compounds 1-3 were found in vitro antitumor activity of 4 compounds. The antibacterial and anti HIV activity test, found that it has a certain antibacterial And the anti HIV activity of.2, studies on chemical constituents and Bioactivities of alstoniascholaris Apocynaceae plant alstoniascholaris gall leaves (Alstonia scholaris), Apocynaceae plants of the genus in Changshan chicken bone, wood material soft delicate, whole plant milk rich, chewing gum can extract raw materials, named "gum tree". Commonly known as "dengtaiye alstoniascholaris leaves" Dai medicine for the treatment of whooping cough, chronic bronchitis and so on. There are now on the market and leaves Yunnan Datang Hanfang Pharmaceutical Co Ltd Kunming Zhenhua pharmaceutical factory production and limited production of dengtaiye particles and other non prescription pharmaceutical products. By five and the total alkaloid drug developed leaf capsule has a cough. Antiasthmatic effect, anti-inflammatory and analgesic, currently a clinical experiment has been completed. As a part of the traditional Chinese medicine research, we cecidium dengtaiye studied chemical composition, from the Communist Party of China Isolation and identification of 21 compounds, including 1 new skeleton drop C-5 indole alkaloid, 19 monoterpene indole alkaloids and 1 lignans.3, chemical composition of Apocynaceae plant gum root research we have studied on the root extract of fucoidan, the liquid phase fingerprint fingerprint atlas and leaves are not the same moreover, skeleton compounds more species have been found in the activity of alstoniascholaris outstanding, with a new found interest and target structure and active substances, we carried out to study the chemical constituents of polysaccharide were isolated from roots, 14 monomer compound.4, Apocynaceae plant gum tree branches on the chemical constituents of alstoniascholaris bark records have headache, colds, fever, pneumonia, whooping cough, chronic bronchitis; cure traumatic bleeding, bone, swelling, sores and preparation of pesticides. The festival, I have to gum tree leaf galls Son, roots of the studies on the chemical constituents of polysaccharide, alkaloid found more skeleton types. In this chapter we study the chemical constituents of alstoniascholaris branches, expected to find abundant alkaloids in compound library alstoniascholaris. Through the systemic study on the chemical constituents were isolated, identified 11 compounds.5, structural diversity of indole alkaloid preparation and biological activity of natural monoterpene indole alkaloid skeleton quantity, but the myriads of changes, they are basically from the strictosidine gene. With Hu Dougan the rearrangement of monoterpenoid indole alkaloid by tryptamine and cracking of loganin in a 1:1 molar ratio in strictosidine synthase function under the Mannich reaction. However, our group in the course of the study on the chemical constituents of Winchia CALOPHYLLA have been found in the tryptamine and split ring loganin at a molar ratio of 1:2 condensation products Alstrostines A and B, which prompted us to think about the diversity of the biosynthetic pathway of indole alkaloids. In this chapter, tryptamine and swertiamarin as substrate, preparation of indole alkaloids, structural diversity, and to explore the synthesis pathway of indole alkaloids, were isolated and identified 24 compounds, including 23 indole alkaloids, of which 19 a new compound. Some indole alkaloids were promotes the differentiation of PC12 cells and promote the activity of intracellular calcium influx, and found 4 compounds could promote the activity of intracellular calcium flow from it.

【学位授予单位】：云南大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q946

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