林生;付芃;沈云亨;叶霁;张中晓;杨献文;李慧梁;柳润辉;徐希科;张卫东;
LIN Sheng;FU Peng;SHEN Yun-heng;YE Ji;ZHANG Zhong-xiao;YANG Xian-wen;LI Hui-liang;LIU Run-hui;XU Xi-ke;ZHANG Wei-dong;College of Pharmacy,Second Military Medical University;State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College;

• 1:第二军医大学药学院
• 2:天然药物活性物质与功能国家重点实验室中国医学科学院北京协和医学院药物研究所

摘要(Abstract)：

运用正相和反相硅胶柱色谱、凝胶柱色谱、大孔吸附树脂柱色谱、反相高效液相色谱等分离和纯化方法,从蜘蛛香乙酸乙酯部位中共分离得到173个化合物。应用一维和二维NMR,UV,IR,MS等波谱方法鉴定了它们的结构,化合物类型涉及环烯醚萜、倍半萜、单萜、三萜、木脂素、黄酮、简单芳香类等,其中新化合物77个。前期已对68个新化合物和25个已知化合物进行了报道。该文报道余下9个新化合物(1~9)和71个已知化合物的分离和结构鉴定,valeriotriate A(8a)的结构修正,以及肿瘤细胞毒活性筛选。
Application of a combination of various chromatographic techniques including column chromatography over silica gel,Sephadex LH-20,macroporous adsorbent resin,and reversed-phase HPLC,led to the isolation of 173 compounds including irdidoids,monoterpenes,sesquiterpenes,triterpenes,lignans,flavonoids,and simple aromatic derivatives from the ethyl acetate-soluble fraction of the whole plants of Valeriana jatamansi(Valerianaceae),and their structures were elucidated by spectroscopic methods including 1D,2D NMR UV,IR,and MS techniques.Among them,77 compounds were new.In previous reports,we have described the isolation,structure elucidation,and bioactivities of 68 new and 25 known compounds.As a consequence,we herein reported the isolation and structure elucidation of the remaining 9 new and 71 known compounds,the structure revision of valeriotriate A(8a),as well as cytotoxicity of some compounds.

关键词(KeyWords)： 败酱科;蜘蛛香;化学成分;细胞毒
Valerianaceae;Valeriana jatamansi;chemical constituents;cytotoxicity

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81522050,81230090,81520108030,21472238);; 上海科学基金项目(12401900801,13401900103,13401900101)

作者(Author): 林生;付芃;沈云亨;叶霁;张中晓;杨献文;李慧梁;柳润辉;徐希科;张卫东;
LIN Sheng;FU Peng;SHEN Yun-heng;YE Ji;ZHANG Zhong-xiao;YANG Xian-wen;LI Hui-liang;LIU Run-hui;XU Xi-ke;ZHANG Wei-dong;College of Pharmacy,Second Military Medical University;State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College;

Email:

DOI: 10.19540/j.cnki.cjcmm.20171027.008

参考文献(References)：

• [1]张振学,姚新生.药用植物缬草的化学研究进展[J].中国药物化学杂志,2000,10(3):226.
• [2]中国药典.一部[S].2015:368.
• [3]李少华,闫智勇.蜘蛛香环烯醚萜类成分的研究进展[J].中国新药杂志,2012,21(6):633.
• [4]陈磊,郑清明,郑汉臣,等.蜘蛛香研究进展[J].中国野生植物资源,2002,21(1):8.
• [5]Lin S,Shen Y H,Li H L,et al.Acylated iridoids with cytotoxicity from Valeriana jatamansi[J].J Nat Prod,2009,72(4):650.
• [6]Lin S,Chen T,Liu X H,et al.Iridoids and lignans from Valeriana jatamansi[J].J Nat Prod,2010,73:632.
• [7]Lin S,Shen Y H,Zhang Z X,et al.Revision of the structures of1,5-dihydroxy-3,8-epoxyvalechlorine,volvaltrate B,and valeriotetrate C from Valeriana jatamansi and V.officinalis[J].J Nat Prod,2010,73:1723.
• [8]Lin S,Fu P,Chen T,et al.Minor valepotriates from Valeriana jatamansi and their cytotoxicity against metastatic prostate cancer cells[J].Planta Med,2015,81:56.
• [9]Lin S,Zhang Z X,Chen T,et al.Characterization of chlorinated valepotriates from Valeriana jatamansi[J].Phytochemistry,2013,85:185.
• [10]Lin S,Chen T,Fu P,et al.Three decomposition products of valepotriates from Valeriana jatamansi and their cytotoxic activity[J].J Asian Nat Prod Res,2015,17(5):455.
• [11]Lin S,Fu P,Chen T,et al.Three minor valepotriate isomers from Valeriana jatamansi and their cytotoxicity[J].J Asian Nat Prod Res,2017,19(1):15.
• [12]Lin S,Ye J,Liang X,et al.Mass spectrometric profiling of valepotriates possessing various acyloxy groups from Valeriana jatamansi[J].J Mass Spectrom,2015,50(11):1294.
• [13]Li X G,Chen T,Lin S,et al.Valeriana jatamansi constituent IVHD-valtrate as a novel therapeutic agent to human ovarian cancer:in vitro and in vivo activities and mechanisms[J].Curr Cancer Drug Tar,2013,13(4):472.
• [14]Bagchi A,Oshima Y,Hikino H.Nardostachin,an iridoid of Nardostachys chinensis[J].Planta Med,1988,54(1):87.
• [15]Yu L L,Huang R,Han C R,et al.New iridoid triesters from Valeriana jatamansi[J].Helv Chem Acta,2005,88:1059.
• [16]Yang B,Zhang J F,Song H Z,et al.Two new iridoid esters from the root and rhizome of Valeriana jatamansi Jones[J].Helv Chem Acta,2015,98:1225.
• [17]Trifilieff E.Isolation of the postulated precursor of nor-patchoulenol in patchouli leaves[J].Phytochemistry,1980,19:2467.
• [18]Ming D S,Yu D Q,Yang Y Y,et al.The structures of three novel sesquiterpenoids from Valeriana jatamansi Jones[J].Tetrahedron Lett,1997,38(29):5205.
• [19]Aleu J,Hanson J R,Hernández R,et al.Biotransformation of the fungistatic sesquiterpenoid patchoulol by Botrytis cinerea[J].J Nat Prod,1999,62(3):437.
• [20]Sun Z H,Hu C Q,Wang J Y.A new sesquiterpene from Caragana intermediia[J].Chin Chem Lett,2007,18:1379.
• [21]Piet D P,Schrijvers R,Franssen M C R,et al.Biotransformation of germacrane epoxides by Cichorium intybus[J].Tetrahedron,1995,51(22):6303.
• [22]Kato T,Tsunakawa M,Sasaki N,et al.Growth and germination inhibitors in rice husks[J].Phytochemistry,1977,16:45.
• [23]Tan S T,Wilkins A L,Holland P T.Isolation and X-ray crystal structure of(E)-4-(r-1',t-2',c-4'-trihydroxy-2',6 trimethylcyclohexyl)but-3-en-2-one,a constituent of New Zealand thyme honey[J].Aust J Chem,1989,42:1799.
• [24]彭双,韩立峰,刘二伟,等.荷叶中化学成分的分离与鉴定[J].沈阳药科大学学报,2012,29(7):519.
• [25]Paulo N B,Otilia D L P,Maria S T,et al.Secondary metabolites of Protium heptaphyllum March[J].Quim Nova,2002,25(6B):1078.
• [26]谭俊杰,蒋山好,朱大元.天山棱子芹化学成分的研究[J].天然产物研究与开发,2005,17(3):267.
• [27]Maldonado E,Apan M T R,Pérez-Castorena A L.Anti-inflammatory activity of phenyl propanoids from Coreopsis mutica var.mutica[J].Planta Med,1998,64:660.
• [28]Glaser J,Schultheis M,Moll H,et al.Antileishmanial and cytotoxic compounds from Valeriana wallichii and identification of a novel nepetolactone derivative[J].Molecules,2015,20:5740.
• [29]Sims J J,Pettus J A.Isolation of free cis and trans-phytol from the red alga Gracilaria andersoni[J].Phytochemistry,1976,15:1076.
• [30]樊晓娜,林生,朱承根,等.小花异裂菊中的萜类成分及其活性[J].中国中药杂志,2010,35(3):315.
• [31]谷海峰,陈若芸,孙玉华,等.香青兰化学成分研究Ⅱ[J].中国中药杂志,2005,30(9):677.
• [32]林生,张中晓,沈云亨,等.菊叶千里光乙酸乙酯部位化学成分研究[J].中国中药杂志,2010,35(9):1137.
• [33]Yang H O,Suh D Y,Han B H.Isolation and characterization of platelet-activating factor receptor binding antagonists from Biota orientalis[J].Planta Med,1995,61:37.
• [34]Gupta S R,Seshadri T R,Sharma C S,et al.Chemical investigation of dikamaligum:isolation of a new flavone,4-hydroxywogonin[J].Ind J Chem,1975,13:785.
• [35]Rodríguez E,Carman N J,Vander Velde G,et al.Methoxylated flavonoids from Artemisia[J].Phytochemistry,1972,11:3509.
• [36]Shen C C.Nuclear magnetic resonance studies of 5,7-dihyroxyflavonoids[J].Phytochemistry,1993,34:843.
• [37]Wasowski C,Marder M,Viola H,et al.Isolation and identificaiton of 6-methylapigen,a competitive ligand for the brain GABAA receptors,from Valeriana wallichii[J].Planta Med,2002,68:934.
• [38]Youssef D T A,Ramadan M A,Khalifa A A.Acetophenones,a chalcone,a chromone and flavonoids from Pancratium maritimum[J].Phytochemistry,1998,49:2579.
• [39]Kuo Y H,Lee S M,Lai J S.Constituents of the whole herb of Clinoponium laxiflorum[J].J Chin Chem Soc,2000,47:241.
• [40]张幸国,田景奎.猫爪草化学成分的研究(Ⅲ)[J].中国药学杂志,2006,41(19):1460.
• [41]Kilidhar S B,Parthasarathy M R,Sharma P.Prinsepiol,a lignan from stems of Prinsepia utilis[J].Phytochemistry,1982,21:796.
• [42]林生,张艳玲,刘明韬,等.小蜡树化学成分的研究[J].中国中药杂志,2015,40(13):2602.
• [43]Miyauchi T,Ozawa S.Formation of(+)-eudesmin in Magnolia kobus DC.var borealis SARG[J].Phytochemistry 1998,47:665.
• [44]Miyazawa M,Kasahara H,Kameoka H.Biotransformation of lignans:a specific microbial oxidation of(+)-eudesmin and(+)-magnolin by Aspergillus niger[J].Phytochemistry,1993,34:1501.
• [45]赵友兴,李承森,罗晓东,等.云南铁杉中一个新的倍半木脂素[J].云南植物研究,2005,27(2):217.
• [46]Sakurai N,Nagashima S,Kawai K,et al.A new lignan,(-)-berchemol,from Berchemia racemosa[J].Chem Pharm Bull,1989,37:3311.
• [47]樊晓娜,林生,朱承根,等.小花异裂菊中的芳香类化学成分及其活性[J].中国中药杂志,2011,36(1):48.
• [48]Pouchert C J,Behnke J.Aldrich library of13C and1H FT NMR spectra[M].USA:Aldrich Chemical Co.,Inc,1992.
• [49]高坤,贾忠建.齿叶橐吾中甾醇类化合物结构研究[J].兰州大学学报,1997,33(4):77.