【作者】 周乐；

【导师】 宋少江；

【作者基本信息】 沈阳药科大学 ， 天然药物化学， 2019， 博士

【摘要】 红树莓(Rubus ideaus L.)为蔷薇科(Rosaceae)悬钩子属(Rubus)多年生的落叶小灌木。其果实色泽鲜艳、营养丰富,深受广大消费者青睐。红树莓干燥的果实,又称覆盆子,作为传统中药在我国已有千年的药用历史。红树莓的全株可入药,民间用于止血、止痢,治疗目赤肿痛、跌打损伤、腮腺炎、扁桃体炎、急慢性肝炎、腰腿疼痛以及风湿骨痛等炎症。在国外,红树莓也被人们作为良好的防病保健水果食品。现代药理研究表明,红树莓能够提高淋巴细胞增殖率,改善机体免疫,改善记忆等功效。本文通过采用多种色谱分离方法,从红树莓干燥果实的70%乙醇提取物中分离得到108个化合物,通过理化常数测定、波谱光谱数据分析、计算ECD和计算NMR等方法,确定了它们的化学结构以及绝大多数化合物的绝对构型。在这些分离得到的化合物中,包括木脂素类82个,黄酮类2个,三萜类2个以及其他类22个。其中44个化合物(A1-A10,A12,A14,A16,A25,A26,A28,A35,A41,A42,A44,A47,A48,A79-A98,A105,A106)为新化合物。对分离得到的木脂素类成分进行结构鉴定过程中,归纳总结了几类常见木脂素的1H NMR快速鉴别方法;此外,针对1,2-二苯基丙烷类结构相对构型的判断方法上,发现了采用1H NMR确定其相对构型的两种新方法,即在极性小的氘代溶剂CDCl3中,利用H2-3亚甲基中两个磁不等同的质子间的化学位移差值的大小判断threo和erythro构型;在极性大的methanol-d4,DMSO-d6和acetone-d6中,利用H-1与H-2的化学位移差值的大小进行相对构型的判断。在对这些化合物的绝对构型的确定的过程中,由于这些具有手性中心的木脂素类成分均以外消旋混合物的形式存在,通过手性拆分的方法进一步得到了一系列光学纯的对映异构体。在此基础上,通过MTT法对分离得到的不同类型木脂素对映异构体进行了神经保护活性的筛选,结果显示,部分对映异构体之间表现出较为明显的活性选择性的差异,进一步的药理机制的研究阐释并讨论了对映异构体之间产生活性差异的原因。草珊瑚[Sarcandra glabra(Thunb.)Nakai],又名肿节风,为金粟兰科(Chloranthaceae)草珊瑚属(Sarcandra)的多年生常绿草本或亚灌木植物。草珊瑚属植物全世界共有3个种,分布于热带及亚热带地区,其中我国有草珊瑚(S.glabra)和海南草珊瑚(S.hainanensis)这2个品种。其分布广泛,药用资源丰富,主产于我国江浙地区以及长江以南各省份。草珊瑚入药的历史悠久,现为《中华人民共和国药典》2005版一部收载的法定药材。利用硅胶柱色谱、聚酰胺柱色谱、HP20柱色谱、开放ODS柱色谱、Sephadax LH-20柱色谱及制备HPLC和手性拆分等方法从草珊瑚的干燥全株80%的乙醇提取物中,共分离出61个化合物,通过分析其理化性质并结合多种谱学手段,鉴定了它们的结构。这些化合物包括10个倍半萜类化合物、5个生物碱类化合物、8个黄酮类化合物、9个香豆素类成分、9个木脂素类结构以及20个其他类结构。其中,B1、B2、B6、B36、B51/B52和B60等7个为新化合物。以上研究内容丰富了草珊瑚的化学成分研究,为草珊瑚的药用价值的开发和应用奠定物质基础。更多还原

【Abstract】 Red raspberry(Rubus ideaus L.),taxonomically belonging to the Rosaceae family and Rubus genus,is a perennial and deciduous shrub.It is popular for its distinctive flavor and attractive red color as well as rich in nutrition,which is favored by consumers.Its air-dried fruit,also called "fu-pen-zi",has been applied as a traditional Chinese medicine for thousands of years.The whole plant of red raspberry can be used as medicine.It is used for hemostasis and dysentery in folk.It can also be used to treat a variety of inflammation diseases,such as swelling and pain of eyes,injury of beating,mumps,tonsillitis,acute and chronic hepatitis,pain of waist,legs,and bones,and rheumatism.Additionally,red raspberry is also regarded as a good health fruit food for disease prevention in foreign countries.Modern pharmacological studies have shown that red raspberry could improve lymphocyte proliferation rate and immune function,and had the function of memory improvement.In this paper,108 compounds were isolated from 70%ethanol extract of air-dried red raspberry fruits by means of various chromatographic separation methods.Their chemical structures and most of the absolute configurations were determined via extensive spectroscopic and spectrometric methods,as well as the calculation of ECD and NMR.Among these isolated compounds,these were 82 lignans and sesquilignans,2 flavonoids,2 triterpenoids and 22 other compounds,and 44 compounds were new,including A1-A10,A12,A14,A16,A25,A26,A28,A35,A41,A42,A44,A47,A48,A79-A98,A105 and A106.In the process of structural identification of these compounds,we have accumulated a lot of analytical experience based on 1H NMR spectroscopy,and summarized several kinds of rapid identification methods of common lignans via 1H NMR.In addition,we found two new convenient and brief methods based on 1H NMR to judging the relative configuration of 1,2-diphenylpropane.The threo and erythro configurations can be determined via the differences of chemical shifts between two protons of H2-3 methylene in the low-polar deuterium solvent CDCl3;in the large-polar deuterium solvents,such as methanol-d4,DMSO-d6 and acetone-d6.the threo and erythro configurations can be determined by the differences of chemical shifts between H-1 and H-2.During our determining the absolute configurations of these compounds,we found that all the lignans with chiral centers existed in the form of racemic mixtures.Subsequently,with the aid of chiral HPLC resolution,a series of optically pure enantiomeric compounds were successfully obtained.Meanwhile,the neuroprotective activities of these enantiomers against H2O2-induced oxidative injury and the possible enantioselective protective mechanism were investigated by MTT using human neuroblastoma SH-SY5Y cells.The results suggested that some of enantiomers exhibit significant differences and the possible mechanisms of the enantiomers were investigated in human neuroblastoma SH-SY5Y cells.Sarcandra glabra(Thunb.)Nakai,also known as zhong-jie-feng,belongs to family Chloranthaceae and Sarcandra genus,which is a perennial evergreen herbs or subshrub.This genus of plants contains three species in the world,which are mainly distributed in tropical and subtropical regions.Among them,S.glabra and S.hainanensis are native to China.It is widely distributed and has abundant medicinal resources,and is mainly grown in Jiangsu and Zhejiang provinces,as well as south of the Yangtze River.Sarcandra glabra has been used as traditional Chinese medicine for thousands of years,and it is now a statutory medicinal material which is recorded in the 2005 edition of the Pharmacopoeia of the People’s Republic of China.By means of various chromatographic methods,61 compounds were isolated from the 80%ethanol extract of the air-dried plants of S.glabra.These compounds were identified by extensive spectroscopic and spectrometric methods,including 10 sesquiterpenoids,5 alkaloids,8 flavonoids,9 lignans,9 coumarins and 20 other compounds.Of all these isolates,7 compounds(B1,B2,B6,B36,B51/B52 and B60)were new compounds isolated from natural plants.The discovery of these compounds enriched the study of the chemical constituents of S.glabra and laid a foundation for the development and application of its medicinal value.更多还原