摘要
茶芎(Ligusticum sinense Oliv. cv. Chaxiong)系伞形科藁本属植物,又名抚芎,是江西特产中药材之一,主产于江西九江地区的瑞昌、武宁、德安等县市。其根茎具有行气活血、祛风止痛之功效,常与川芎混用。茶芎的化学成分研究报道发现其根茎中的化学成分与川芎类似,主要是苯酞类成分。茶芎的地上部位在当地一直没有得到开发而被丢弃,而且文献调研也未有关于茶芎地上部位的化学成分及药理活性的报道。为了从植物资源中寻找类型多样、结构新颖、活性显著地次级代谢产物,同时也为了阐明同种植物不同部位化学成分差异,充分开发利用药用资源,本论文对茶芎地上部位的乙醇提取物进行了系统的化学成分分离和结构鉴定,并通过与药理学人员合作,对分离得到的单体化合物的活性进行了初步的药理活性筛选。
运用硅胶、大孔树脂、凝胶Sephadex LH-20.中压液相色谱及高效制备液相色谱等各种色谱分离手段,从茶芎的95%乙醇提取物中,分离得到了88个化合物,并结合MS、 UV、 IR、 ID NMR、2D NMR和CD等波谱分析及化学方法,鉴定了它们的结构(化合物的名称见Table1,结构见Fig.1),包括苯酞单体19个,苯酞二聚体8个,苯酞糖苷类6个,酚苷类2个,黄酮类6个,奎尼酸类9个,倍半萜类11个,香豆素类5个,生物碱类3个,三萜类2个,其他类17个。其中新化合物24个(9*、15*、16*、18*、20*、25*、26*、33*、37*-43*、48*、49*、52*、53*、59*、64*、65*、67*、72*),新的天然产物5个(2**、7**、13**、27**、71**)。其中化合物37*-39*为首次发现的藁本内酯与新蛇床内酯通过环加成反应形成的苯酞二聚体类化合物,丰富了苯酞二聚体的结构类型,并首次利用计算ECD的方法确定其绝对构型。
运用多种药理模型对所分离得到的化合物进行了活性筛选,其中化合物9‘、25*、33*、37*、46和52*在10μM浓度下对氧糖剥夺的神经元细胞有一定的保护活性；化合物38*和41*对HELA细胞株的IC50分别为22.29μM和14.52μM,显示出一定的细胞毒活性;化合物7**、9*、25*、36和50对半乳糖胺引起的HL-7702细胞损伤有一定的保护活性；化合物9*、15*和52*对APAP引起的HepG2细胞损伤有显著地保护作用。
Chaxiong belongs to the species of Ligusticum of the Umbelliferae family, which is endemic to Jiangxi province. The rhizome of it has been used as the substitute for Chuanxiong. The preliminary study of rhizome of Chaxiong have found that there are the similary component as Chuanxiong, mainly the mono-and dimeric-phthalides. The aerial parts of Chaxiong have always been thrown away without any research. In order to find novel compounds with new structures and significant activities, to explain the different chemical constituents in different parts of the same plant, we conducted the chemical research to the95%ethanol extracts of the aerial parts of Chaxiong. The bioactivities of the purified compounds were test on several pharmacological models with the support of pharmacological staff.
Based on a variety of chromatographic techniques, eighty-eight compounds have been isolated from an ethanol extract of the aerial parts of Chaxiong, and their structures were elucidated by spectroscopic methods (Names and structures of the purified compounds are listed in Table1and Fig.1). These compounds included nineteen mono-phthalides, eight phthalide dimmers, six phthalide glycosides, two phenolic glycosides, six flavonoids, nine quinic acids, eleven sesquiterpenoids, five coumarins, three triterpenes and seventeen other types of compounds. Among them, compounds9*,15*,16*,18*,20*,25*,26*,33*,37*-43*,48*,49*,52*,53*,59*,64*,65*,67*and72*were new compounds and compounds2**,7**,13**,27**and71**were new natural products. Notably, new compounds37*-39*were the first report about the phthalide dimmers comprising of ligustilide and sedanolide, which enriched the phthalide dimmers types.
In the in vitro assays, compounds9*,25*,33*,37*,46and52*have showed moderate protective effect against neuronal impairment induced by deprival of oxygen and glucose at10μM. Compounds38*and41*showed some extent of cytotoxcity against Hela cell line with IC50of22.29μM and14.52μM, respectively. Compounds7**,9*,25*,36and50exhibited moderate hepatoprotective activities against D-galactosamine-induced HL-7702cell damage. Compounds9*,15*and52*showed obviously hepatoprotective activities against APAP-induced HepG2cell damage.
引文
[1]Zhao L. Q. Research advancement on terpenoids in ligusticum and their biological activity [J]. Lishizhen Medicine and Material Research,2006,17:16-18.
[2]Kobayashi M., Fujita M., Mitsuhashi H. Studies on the constituents of Umbelliferae plants XV:Constituents of cnidium officinale:Occurrence of pregnenolone coniferylferulate and hydroxyphthalides[J]. Chem. Pharm. Bull.1987,35(4):1427-1433.
[3]Li S. L., Chan S. S. K., Lin G., Ling L., Yan R., Chung H. S., Tam Y. K. Simultaneous analysis of seventeen chemical ingredients of Ligusticum Chuanxiong by on-line high performance liquid chromatography-diode array detector-mass spectrometry[J]. Planta Medica,2003,69(5):445-451.
[4]Lu G. H., Chan K., Liang Y. Z., Leung K., Chan C. L., Jiang Z. H., Zhao Z. Z. Development of high-performance liquid chromatographic fingerprints for distinguishing chinese Angelica from related Umbelliferae Herbs[J]. J.Chromatogr. A, 2005,1073:383-392.
[5]Kobayashi M., Mitsuhashi H. Studies on the constituents of Umbelliferae plants. XVII. Structures of three new ligustilide derivatives from Ligusticum wallichii[J]. Chem. Pharm. Bull.,1987,35(12):4789-4792.
[6]Naito T., Katsuhara T., Niitsu K., Ikeya Y., Okada M, Mitsuhshi H. Two phthalides from Ligusticum chuanxiong[J], Phytochemistry,1992,31(2):639-642.
[7]Wang P. S., Gao X. L., Wang Y. X., Yoshiyasu F., Iwao M., Michiharu S. Phthalides from the Rhizome of Ligusticum wallichii[J]. Phytochemistry,1984,23(9):2033-2038
[8]Ogawa Y, Hosaka K., Chin M., Mitsuhashi H. Synthesis of (Z)-3-Butylidene-6, 7-dihydroxyphthalide[J]. Heterocycles,1991,32(9):1737-1744.
[9]Takashi N., Yukinobu I., Minoru O., Mistuhashi H. Two phthalides from Ligusticum chuanxiong[J]. Phytochemisrty,1996,41(1):233-236
[10]Takashi N., Kazuaki N., Yukinobu I., Minoru O., Mistuhashi H. A phthalide and 2-Farnesyl-6-methyl benzoquinone from Ligusticum chuanxiong[J]. Phytochemistry, 1992,31(5):1787-1790.
[11]Regina B., Katrin von D., Gernot J., Willi S., Heide T. R. Interference of plant extracts, phytoestrogens and antioxidants with the MTT Tetrazolium assay[J]. Planta medica,2003,69(5):445-451.
[12]Huang J., Lu X. Q., Zhang C, Lu J., Li G. Y, Lin R. C, Wang J. H. Anti-inflammatory Ligustilides from Ligusticum chuanxiong Hort.[J]. Fitoteropia, 2013,91:21-27.
[13]Tsuchida T., Kobayashi M., Kaneko K., Mitsuhashi H. Studies on the constituents of Umbelliferae Plants. XVI. Isolation and structures of three new ligustilide derivatives from Angelica acutioba[J]. Chem. Pharm. Bull.,1987,35(11):4460-4.
[14]Tsuchida T., Kobayashi M., Kaneko K., Mitsuhashi H. Phthalide dimmers from Ligusticum chuanxiong Hort.[J]. Heterocycles,1991,32(12):2433-2442.
[15]Kaouadji M., Pachtere F. D., Pouget C, Chulia A. J., Lavaitte S. Three Additional Phthalide Derivatives, an Epoxymonomer and Two Dimmers from Ligusticum wallichii Rhizomes[J]. J Nat. Prod.,1986,49(5):872-877.
[16]Delgado G., Reza-Garduno R. G., Toscano R. A., Bye R., Linares E. Secondary metabolites from the roots of Ligusticum porteri (Umbelliferae)[J]. Heterocycles, 1988,27(6):1305-12.
[17]Li Y. H., Peng S. L., Zhou Y, Yu K. B., Ding L. S. Two new phthalides from Ligusticum chuanxiong[J]. Planta Medica,2006,72(7):652-656.
[18]Zhao L. Q. Research Advancement on terpenoids in Ligusticum and their biological activity[J]. Lishizhen Medicine and Material Research,2006,17:16-18.
[19]Chen R.Y. Research on the chemistry and pharmacology of L.sinense Oliv [J]. Trad. Chin. Med. J.,2002,1:44-48.
[20]Miao C. P, Wu S. H. A new sesquiterpenoid from Ligusticum chuanxiong Hort. [J]. Fitroteapia,2010,81:1088-1090.
[21]Xiao Y. Q., Li L. Studies on chemical constituents of the Rhizome of Ligusticum chuanxiong [J]. China Journal of Chinese Materia Medica,2002,27(7):519-522.
[22]Gao Y. L., Wang W. J. The chemical constituents of Ligusticum calophlebicum[J]. Acta Botanica Yunnanica,2004,26:234-236.
[23]Taro K. Coumarins from the roots of Ligusticum multivittatum[J]. J. Nat. Med., 2008,62:87-90.
[24]Ren D. C, Qian S. H. Chemical study on aerial parts of Ligusticum chuanxiong[J]. China Journal of Chinese Materia Medica,2007,3:1418-1420.
[25]Ren D. C, Qian S. H. Chemical study on aerial parts of Ligusticum chuanxiong[J]. China Journal of Chinese Materia Medica,2008,33:2417-2418.
[26]Li Q. Y, Gan G. R, Liu Y. W. Research advancement on the components and pharmacology of Ligusticum chuanxiong[J]. Lishizhen Medicine and Material Research.2006,17(7):1298-1299.
[27]Fan Z. C. Polysaccharides from Ligusticum chuanxiong[J]. Chinese Traditional and Herbal Drugs,2006,37:973-976.
[28]Mitsuhashi H., Nomura M. Studies on the constituents of Umbelliferae Plants XII. biogenesis of 3-Butylphthalide[J]. Chem. Pharm. Bull.,1966,14(7):777-778.
[29]陈耀祖,段志兴,张慧迪 岷山当归化学成分及药效的研究[J].兰州大学学报(自然科学版),1984,20(1)：158.
[30]Chen K. J., Chen K. Ischemic stroke treated with Ligusticum chuanxiong[J]. Chin. Med. J.1992,105(10):870-873.
[31]Beck J. J., Stermitz F. R. Addition of methyl thioglycolate and benzylamine to (Z)-ligustilide, a bioactive unsaturated lactone constituent of several herbal medicines. An improved synthesis of (Z)-ligustilide[J]. J. Nat. Prod.1995,58(7): 1047-1055
[32]Miyazama M., Tsukamoto T., Anzai J., Ishikawa Y. Insecticidal effect of phthalides and furanocoumarins from Angelica acutiloba against Drosophila Melanogaster[J]. J. Agric. Food Chem.2004,52:4401-4405.
[33]Liu L., Ning Z. Q., Shan S., Zhang K., Deng T., Lu X. P., Cheng Y. Y. Phthalide lactones from Ligusticum chuanxiong inhibit lipopolysaccharide-induced TNF-a production and TNF-a mediated NF-kB activation[J]. Planta Medica,2005,71(9): 808-813.
[34]Ka M. H., Choi E. H., Chun H. S., Lee K. G. Antioxidative activity of volatile extracts isolated from Angelica tenuissimae roots, peppermint leaves, Pine needles, and sweet flag leaves[J]. J. Agric. Food Chem.2005,53(10):4124-4129.
[35]Long R., Yang F., Du J. R., Qian Z. M., Wang C. Y, Chen C. Effects of ligustilide on tumor growth and immune function in institute of cancer research mice[J]. Tropical Journal of pharmaceutical research 2012,11(3):421-428.
[36]Zhong J., Pollastro F., Prenen J., Zhu Z. M., Appendino G., Nilius B. Ligustilide:a Novel TRPA1 modulator[J]. Eur. J. Physiol.2011,462:841-849.
[37]Qi H.Y., Han Y. F., Rong J. H. Potential roles of P13K/Akt and Nrf2-Keapl pathways in regulating hormesis of Z-ligustilide in PC12 cells against oxygen and glucose deprivation[J]. Neuropharmacology,2012,62:1659-1670.
[38]冯亦璞,胡盾,张丽英丁基苯酞对小鼠全脑缺血的保护作用[J].药学学报,1995,30：741.
[39]刘小光,冯亦璞丁苯酞对局部脑缺血大鼠行为和病理改变的保护作用[J].药学学报,1995,30：896.
[40]Deng W. B., Feng Y. P. Effect of dl-Butylphthalide on brain edema in rats subjected to focal cerebral ischemia[J]. Chin. Med. Sci. J.,1997,12:102.
[41]Yan C. H., Feng Y. P., Zhang J. T. Effects of dl-3-n-butylphthalide on regional cerebral blood flow in middle cerebral artery occlusion rats[J]. Acta Pharm. Sinica, 1998,19:117.
[42]罗艳利,王瑞玲,魏娟红丁苯酞对急性脑梗死患者血清C-反应蛋白的影响[J].中国实用内科杂志,2007,27(13)：1045-1046.
[43]Chong Z. Z., Feng Y. P., Effects of dl-3-n-butylphthalide on production of TXB2 and 6-keto-PGF1 in rat brain during focal cerebral ischemia and reperfusion [J]. Acta pharm. Sinica,1997,18(6):505-508.
[44]Xiong J., Feng Y. P. Effects of butylphthalide on the activities of complexes of the mitochondrial respiratory chain[J]. Acta Pharm. Sinica,1999,34(4):241-245.
[45]Xu H. L., Feng Y. P. Effects of 3-n-butylphthalide on thrombosis formation and platelet function in rats[J]. Acta Pharm. Sinica,2001,36(5):329-333.
[46]Xiao X. J., Qi Y. C, Gao Z. S., Li Q., Guo Z. C, Lv P. Y. Effects of 3-n-butylphthalide on learning-memory ability and Na+-K+-ATPase activity of mitochondria in rats with chronic cerebral hypoperfusion[J]. Chin. J. Behav. Med& Brain Sci.2011,20(8):688-690.
[47]Liang J. H., Wei L. Y., Tang X. C. Butylphthalide in the protection of focal cerebral ischemis-reperfusion in rats by enhancing the antioxidant activity [J]. Int. J. Cerebrovasc. Dis.2013,21(3):186-188.
[48]Deng S. X., Chen S. N., Lu J., Nikolic D. GABAergic phthalide dimers from Angelica sinensis (Oliv.) diels[J]. Phytochemical Analysis 2006,17(6):398-405.
[49]Chen, F, Wang, T, Wu, Y. F. Use of phthalide dimmers for antitumor[P]. U. S. 8247444 B2,2012.
[50]Zhou Y, Talor B., Smith T. J., Liu Z. P., Clench M., Davies N. W., Rainsford K. D. A novel compound from celery seed with a bactericidal effect against Helicobacter pylori [J]. J. Pharm. Pharmaco.2009,61(8):1067-1077.
[51]Wan J. Y, Ye D. Y, Wu P. Effect of tetramethylpyrazine on lipopolysaccharides induced macrophage cyclo-oxidase-2 expression and apoptosis of cardiac myocytes[J]. Chin. J. Integrated Trad. West Med.,2004,24(10):906-911.
[52]Shu B., Zhou C. J., Ma Y H., Wang Y J., Shi Q. Research progress on pharmacological activities of the available compositions in Chinese medicinal herb Ligusticum chuanxiong[J]. Chin. Pharm. Bull.2006,22(9):1043-1047.
[53]Yang L., Chen J., Wang W. J., Jin R. Effect of ligustrazine onThl/Th2 imbalance in asthmatic rats[J]. Jiangsu Med. J.2004,30(11):822-823.
[54]Li Z. C, Li L., Yan H. X. Effect of tetramethylpyrazine on the responses of respiration and expression of nNOS in brainstem to hypoxia in rats [J]. Acta Phys. Sinica.2005,57(2):147-153.
[55]Peng A., Ye H. J. Reverse effects of tetramethyl pyrazine on the malignant phenotype of Bel-7402 human hepatocarcinoma cells[J]. Chin. J. Clini. Hepatol. 2002,18(3):157-158.
[56]Liu Z. F., Sun H. Y, Liu W. L. Study on the effects of ligustrazine on recovery of hematopoiesis in acutei radiation injured mice[J]. Chin. J. Radiol. Med. Prot.2004, 24(5):396-398.
[57]Xing Y, Xu J. T., Zhang W. H., Yan M. Effects of ligustrazine on insulin secretion of pancreatic islets in vitro in new-born rats[J]. J. Zhengzhou University (Medical Sciences),2004,39(3):446-447.
[58]陈光娟,沈雅琴,马树德藁本中性油的药理研究Ⅱ对肠和子宫平滑肌的抑制 作用[J].中药通报,1987,12(4)：240.
[59]汤臣廉,许青媛藁本中性油对耐缺氧的影响[J].中国中药杂志,1992,17(12)：745-746.
[60]于德泉常用中药藁本中新化合物的结构合成及活性研究[J].有机化学,1997,17：24.
[1]罗永明茶芎的研究进展[J].江西中医学院学报,1998,10：87-89.
[2]Mclure C. K., Jung K. Y. Pentacovalent oxaphosphorane chemistry in organic synthesis.2. Total synthesis of (±)-tans-and (±)-cis-neocnidilides[J]. J. Org. Chem. 1991,56:2326-2332.
[3]Ohtani I., Kusumi T., Kashman Y., Kakisawa H. High-field FT NMR application of Mosher's method. The absolute configurations of marine terpenoids[J]. J. Am. Chem. Soc.1991,113:4092-4096.
[4]Diaz J. G. Sesquiterpene lactones and other constituents of Mikania Rimachii and Mikania Microptere[J]. Phytochemistry,1992,32(2):597-608.
[5]Huang J., Lu X. Q., Zhang C., Wang J. H. Anti-inflammatory ligustilides from Ligusticum chuanxiong Hort.[J]. Fitoterpia,2013,91:21-27.
[6]Kitajima J., Ishikawa T., Satoh M. Polar constituents of celery seed [J]. Phytochemistry,2003,64:1003-1011.
[7]Tsuchida, T, Kobayashi, M., Kaneko, K., Mitsuhashi, H. Studies on the constituents of Umbelliferae plants.XVI.isolation and structure of three new Iigustilide derivatives from Angelica acutiloba[J]. Chem. Pharm. Bull.1987,35,4460-4464.
[8]Ying, B. P., Qin, G. W., Xu, R. S. Application of CDexciton chirality method in organic chemistry[J]. Chin. J. Org. Chem.1987,3,165-173.
[9]Kaouadji M., Pachtere F. D., Pouget C., Chulia A. J., Lavaitte S. Three Additional Phthalide Derivatives, an Epoxymonomer and Two Dimmers from Ligusticum wallichii Rhizomes[J]. J. Nat. Prod.,1986,49(5):872-877.
[10]Kobayashi M., Mitsuhashi H. Studies on the Constituents of Umbelliferae Plants. XVⅡ. Structures of Three New Ligustilide Derivatives from Ligusticum wallichii[J]. Chem. Pharm. Bull.,1987,35(12):4789-4792.
[11]Bjeldanes L. F., Kim I. S. Phthalide components of Celery essential oil[J]. J.Org. Chem.1977,42(13):2333-2335.
[12]Ping W., Wang H. F., William F. Syhthesis and platelet aggregation inhibitory effects of Harman and phthalide derivatives related to Ligusticum chuanxiong Hort. constituents[J]. Med. Chem. Res.,1997,7(3):180-191.
[13]Ferdinand B., Harold R. Natural occurring terpene derivatives part 338.eudesmanolides and helianolides from Calea rotundifolia[J]. Phytochemistry, 1981,20(7):1635-1637.
[14]Timonen J. M., Nieminen R. M, Sareila O. Synthesis and anti-inflammatory effects of a series of novel 7-hydroxycoumarin derivatives[J]. Eur. J. Med. Chem.,2011, 46(9):3845-3850.
[15]Huang S. X., Yang J., Sun H. D. Three novel terpenoids from Schisandra pabescens var. pubinervis[J]. Helv. Chim. Acta,2006,89(6):1169-1175.
[16]Alfredo O., Emma M. A tris-norsesquiterpene lactone and other sesquiterpenes from Calea crocinervosa[J]. Phytochemistry,1989,28(10):2735-2736.,
[17]Machida K., Kikuchi M. Norisoprenoids from Viburnum dilatatum[J]. Phytochemistry,1996,41(5):1333-1336.
[18]Chen G., Jin H., Li X., Zhang Q., Yan S. Chemical constituents from Rhododenron spinuliferum[J]. Chem. Nat. Comp.,2009,45(5):185-198.
[19]Demin P., Rounova O., Grunberger T. Synthesis of new antiproliferative compounds with an extendol conjugation[J]. Bioorg. Med. Chem.,2004,12(11):3019-3026.
[20]Gonzalez A. G., Arancibia L. Humulenes and other constituents of Ferula Latipinna[J]. J. Nat. Prod.1988,51(6):1140-1147.
[21]D'Abrosca B., Fiorentino A. Structure elucidation and phytotoxicity of C13 nor-isoprenoids from Cestrum parqui[J]. Phytochemistry,2004,65:497-505.
[22]Hammami S., Jannet H. B., Mighri Z. Isolation and structure elucidation of a flavanone, a flavanone glycoside and vomifoliol from Echiochilon Fruticosum growing in Tunisia[J]. Molecules,2004,9:602-608.
[23]Mitsudera H. Malononitrile compounds and use thereof, US 7541374B2.
[24]Saalfrank R.W., Hafner W., Markmann J., Bestmann H. J. Convenient synthesis of 5-alkylidene-2(5H)-furanones,2(5H)-furanones and 2-ethoxyfurans[J], Tetrahedron, 1983,44(16):5095-5100.
[25]Makino M., Endoh T., Fujimoto Y. Studies on the metabolites of Penicillium vulpinum[J]. Heterocycles,1998,48(9):1931-1934.
[26]郭文生,吕扬利用主客体分子包结现象选择分离蛇床子有效成分的方法[J].药学学报,1994,29(11)：829-834.
[27]Razdan T. K., Waight E. S. Chromones and coumarins from Skmmia Lavereoca[J]. Phytochemistry,1987,26(7):2063-2069.
[28]Ciucci D., Vergamini P., Rossi R., Bellina F. Regioselective synthesis of natural and unnatural (Z)-3-(1-alkylidene)phthalide and 3-substituted isocoumarins starting from methyl 3-hydroxybenoztes[J]. Tetrahedron,2000,56(2000):2533-2545.
[29]Naito T., Katsuhare T., Niitsu K. Phthalide dimmers from Ligusticum chuanxiong Hort.[J].Heterocycles,1991,32(12):2433-2442.
[30]Li S. B., Wang Z. W., Fang X. P., Li Y. L. A convenient approach for synthesis of (Z)-3-butylidenephthalide derivatives[J]. Syn. Commun.,1997,27(10):1783-1791.
[31]Kwon J. H., Ahn Y. J. Acaricidal activity of butylidenephthalide identified in Cnidium officinale Rhizome against Dermatophagoides farina and Dermatophagoides pteronyssinus (Acari:Oyroglyphidae)[J]. J. Agric. Food Chem.2002,50:4479-4483.
[32]Wu Z. J., Shen Y. H., Zhang W. D. Chemical constituents of Ainsliaea macrocephala [J]. Chem. Nat. Comp.,2013,49(1):167-169.
[33]Tsukamoto H., Hisada S., Nishibe S. Coumarin and secoiridoid glucosides from Bark of Olea Africana and Olea capensis[J]. Chem. Pharm. Bull.1985,33(1): 396-399.
[34]Yajima A., Oono Y., Nakagawa R., Nukada T., Yabuta G. A simple synthesis of four stereoisomers of roseoside and their inhibitory activity on leukotriene release from mice bone marrow-derived cultured mast cells[J]. Bioo. Med. Chem.,2009,17(1): 189-194.
[35]Ishikawa T., Kondo K., Kitajima J. Water-soluble constituents of Coriander[J]. Chem. Pharm. Bull.2003,51(1):32-39.
[36]Okuyama T., Hosoyama K., Hiraga Y, Kurono G., Takemoto T. The constituents of Osmunda spp. II. A new flavonol glycoside of Osmunda asiatica[J]. Chem. Pharm. Bull.1978,26(10):3071-3074.
[37]Sang S., Lapsley K., Jeong W. S., Lachance P. A., Ho C. T., Rosen R.T. Antioxidative phenolic compounds isolated from Almond Skins. J. Agric. Food Chem.2002,50:2459-2463.
[38]Jin H. Z., Chen G., Li X. F., Zhang W. D. Flavonoids from Rhododendron decorum[J]. Chemistry of Natural Compounds,2009,45(1):85-87.
[39]殷志琦,赵守训 贯叶连翘的化学成分研究[J].中草药,2001,32(6)：487-488.
[40]Gentry E. J., Jampani H. B., Keshavarz-Shokri A., Morton M. D., et al. Antitubercular natural products:berberine from the roots of commercial Hydrastis Canadensis powder. Isolation of inactive 8-oxotetrahydrothalifendine, canadine, hydrastine and two new quinic acid esters, hycandinic acid esters-1 and-2[J]. J. Nat. Prod.,1998,61(10):1187-1189.
[41]Chen Z., Liu Y. M., Yang S., Xu G. F. Studies on the chemical constituents and anticancer activity of Saxifraga stolonifera (L) Meeb[J]. Bio. Med. Chem.,2008,16: 1337-1344.
[42]Zhu Y., Zhang L. X., Zhao Y., Huang G. D. Unusual sesquiterpene lactones with a new carbon skeleton and new acetylenes from Ajania przewalskii[J]. Food chemistry, 2010,118(2):228-238.
[43]Lin Y. L., Lu C. K., Huang Y. J., Chen H. J. Antioxidative caffeoylquinic acids and flavonoids from Hemerocallis fulva flowers[J]. J. Angric. Food Chem.2011,59(16): 8789-8795.
[44]Miyase T., Ueno A., Takizawa N., Kobayashi H. Studies on the glycosides of Epimedium grandifiorum MORR.var.thunbergianum[J]. KarasawaH. Chem. Pharm. Bull.1987,35(3):1109-1117.
[45]Fiorentino A., Greca M.D., Golino A., Monaco P. Unusual sesquiterpene glucosides from Amaranthus retroflexus[J]. Tetrahedron,2006,62:8952-8958.
[46]Xiang W.J., Guo C.Y., Ma L., Hu L.H. Dammarane-type glycosides and long chain sesquiterpene glycosides from Gynostemma yixingense[J]. Fitoterapia,2010,81(4): 248-252.
[47]Lee K., Kim K. H., Ryu S. Y, Lee K. R. Two new sesquiterpene glucosides from Gymnaster koraiensis[J]. Heterocycles,2009,78(11):2827-2835.
[48]Cho D. H., Song S. H., Jang D. O. A method for preparation of unnatural (R)-malic acid derivatives with phenylsilanes[J]. Synth. Commun.,2003,33(4):515-519.
[49]Basnet P., Matsushige K., Hase K., Kadota S., Namba T. Potent antihepatotoxic activity of dicaffeoyl quinic acids from PropoIis[J]. Biol. Pharm. Bull.,1996,19(4): 655-657.
[50]Um B.H., Polat M., Lobstein A., Anton R. A new dicaffeoylquinic acid butyl ester from Isertiapittieri[J]. Fitoterapia,2002,73(6):550-552.
[51]Xiang T., Xiong Q. B., Ketut A., Tezuka Y., Nagaoka T., Wu L. J. Studies on the hepatocyte protective activity and the structure-activity relationships of quinic acid and caffeic acid derivatives from the flower buds of Lonicera bournei[J]. Planta Medica, 2001,67(4):322-325.
[52]Peng L.Y., Mei S.X., Jiang B., Zhou H., Sun H. D. Constituents from Lonicera japonica[J]. Fitoterpia,2000,71(6):713-715.
[53]Zhang J. M., Shi X. F., Ma Q. H., Lin D.Y. Chemical constituents from pine needles ofCedrus deodara[J]. Chem. Nat. Compd.,2011,47(2):272-274.
[54]马柱坤,戴源,张蓓蓓,廖志新高山大戟化学成分的研究[J].西北药学杂志,2012,27(1)：1-4.
[55]李娟,阮汉利,张悦,吴继洲湖北大戟根中的环阿尔廷型三萜[J].天然产物研究与开发,2007,19：995-997.
[56]Liu Q., Chen C. J., Shi X., Zhang L., Chen H.J., Gao K. Chemical constituents from Aphanamixis grandifolia[J]. Chem. Pharm. Bull.,2010,58(11):1431-1435.
[57]Maurer S., Liu W., Zhang X. J., Jiang Y. W., Ma D. W. An efficient synthesis of phenol via CuI/8-hydroxyquinoline-catalyzed hydroxylation of aryl halides and postassium hydroxide[J]. Synlett,2010,6:976-978.
[58]石建功,贾忠建,李瑜风毛菊化学成分研究(I)[J].高等学校化学学报,1991,12(7)：906-909.
[59]王佳,苏亚伦茶芎化学成分研究[J].中药材,2011,34(3)：378-380.
[60]Gonzalez A. G., Bermejo J., Diaz J. G., Arancibia L. Humulenes and other constituents of Ferula Latipinna[J]. J. Nat. Prod.,1988,51(6):1140-1147.
[61]Xiao Z. P., Shi D. H., Li H. Q. Polyphenols based on isoflavones as inhibitors of Helicobacter pylori urease. Bioorg. Med. Chem.,2007,15(11):3703-3710.
[62]Ohtani I., Kusumi T., Kashman Y., Kakisawa H.High-field FT NMR application of Mosher's method. The absolute configurations of marine terpenoids[J]. J. Am. Chem. Soc.1991,113:4092-4096.