摘要
本研究论文对两种药用植物的化学成分及其生物活性进行了系统研究。
1.沙生蜡菊[Helichrysum arenarium(L.)Moench]为菊科蜡菊属植物,主要分布于我国的新疆及国外的俄罗斯、蒙古及欧洲一些国家。在欧洲,沙生蜡菊为传统的植物药,主要作为保肝利胆剂,并具较好的解毒功效,现代药理学研究证明,沙生蜡菊还具有抗氧化、抗菌的作用;以前报道其化学成分主要为黄酮和酚酸类化合物。
对沙生蜡菊(H.arenarium)全草的70%乙醇提取物用溶剂分步萃取法和硅胶柱色谱、制备薄层色谱、聚酰胺色谱、开口ODS柱色谱、高效液相色谱、SephadexLH-20柱色谱及重结晶等分离纯化手段,得到41个化合物。通过理化常数、化学方法及波谱数据(UV、IR、NMR、MS)分析等,鉴定了它们的结构,其中包括19个黄酮类、12个有机酚酸及其酯类、2个异苯并呋喃-1(3H)-酮类、1个香豆素类、1个吡喃-2-酮类及6个其它类成分。
已鉴定的化合物分别为:芹菜素(apigenin,1),芹菜素-7-O-β-D-吡喃葡萄糖苷(apigenin-7-O-β-D-glucopyranoside,2),山柰酚(kaempferol,3),山柰酚-3-O-β-吡哺葡萄糖苷(kaempferol-3-O-β-D-glucopyranoside,4),山柰酚-7-O-β-D-吡喃葡萄糖苷(kaempferol-7-D-β-D-glucopyranoside,5),山柰酚-7-O-α-L-鼠李糖苷(kaempferol-7-O-α-L-rhamnoside,6),木樨草素(luteolin,7),木樨草素-7-O-β-D-吡喃葡萄糖苷(luteolin-7-O-β-D-glucopyranoside,8),槲皮素(quercetin,9),槲皮苷(quercitrin,10),芦丁(rutin,11),柚皮素(naringenin,12),鹰嘴豆芽素(5-hydroxy-4'-methoxyisoflavone,13),绛紫香苷(5-hydroxy-4'-methoxyisoflavone-7-O-β-D-glucopyranoside,14),6,8-二甲氧基-3,5,7-三羟基黄酮(6,8-dimethoxy-3,5,7-trihydroxyflavone,15),3,5-二羟基-6,7,8-三甲氧基黄酮(3,5-dihydroxy-6,7,8-trimethoxyflavone,16),5,6,4'-三羟基黄酮-7-O-β-D-吡喃葡萄糖苷(5,6,4'-trihydroxyflavone-7-O-β-D-glucopyranoside,17),5,4'-二羟基-6,7,3',5'-四甲氧基黄酮(5,4'-dihydroxy-6,7,3',5'-tetramethoxyflavone,18),5,7,4'-三羟基-8-甲氧基黄酮(5,7,4'-trihydroxy-8-methoxyflavone,19),4-羟基-6,7-二甲氧基-1-萘酸(6,7-dimethoxy-4-hydroxy-1-naphthoic acid,20),咖啡酸(caffeic acid,21),咖啡酸甲酯(methyl caffeate,22),原儿茶酸(protocatechuic acid,23),对羟基苯甲酸(p-hydroxybenzoic acid,24),熊果苷(arbutin,25),异香草酸(isovanillic acid,26),没食子酸(gallic acid,27),奎宁酸(quininic acid,28),奎尼酸甲酯(methyl quinic ester,29),绿原酸(caffeotannic acid,30),1,3-O-二咖啡酰基奎尼酸(1,3-O-dicaffeoylquinic acid,31),(Z)-5-hydroxy-7-methoxy-4-[3-methyl-4-(O-β-D-xylopyranosyl)but-2-enyl]isobenzofuran-1(3H)-one(32),5-hydroxy-7-O-β-D-glucopyranosyl-isobenzofuran-1(3H)-one(33),东莨菪内酯(scopoletin,34),6-(4'-hydroxy-trans-styryl)-4-methoxy-2-pyrone(35),鲨肌醇(scyllo-inositol,36),白桦酸(betulic acid,37),齐墩果酸(oleanolic acid,38),熊果酸(ursolic acid,39),β-谷甾醇(β-sitosterol,40),胡萝卜苷(daucosterol,41)。其中化合物20,32为未见文献报道的新化合物,化合物6,13,14,17,18,26,29,33,37为首次从本属植物中分离得到。
对沙生蜡菊提取物、萃取层及单体化合物做了抗菌、体外抗肿瘤及抗炎三方面的活性筛选。
利用文献,针对具有抗肿瘤和抗菌消炎作用的活性天然产物,在其结构修饰及人工合成方面的研究进展做了综述。
2.蓝刺头(Echinops latifolius Tausch)又名火球花,为菊科蓝刺头属植物,多年生草本,分布于我国黑龙江、吉林、辽宁、河北、河南、山西、内蒙古、江苏及湖北等地。药用其根,为中药禹州漏芦所属的二种基源植物之一,其味苦,性寒,入胃经。禹州漏芦中含有噻吩、三萜、挥发油等化学成分,具有抗肿瘤、抗病毒、抗真菌、抗炎及保肝作用等活性。
目前,对蓝刺头地上部分的化学成分及药理活性的研究报道很少,为寻找新的活性成分,扩大药用部位,我们决定对蓝刺头地上部分(包括茎叶和花)进行系统的化学成分研究。
本文对蓝刺头(E latifolius)地上部分的95%乙醇提取物化学成分进行了系统研究,利用硅胶吸附柱色谱、制备薄层、Sephadex LH-20柱色谱等分离手段,从蓝刺头地上部分得到14个化合物。通过理化性质、化学反应以及波谱方法鉴定了它们的结构,分别为:β-谷甾醇(β-sitosterol,1),蓝刺头碱(echinopsine,2),蒲公英萜醇乙酸酯(taraxerol acetate,3),胡萝卜苷(daucosterol,4),α-三联噻吩(α-terthienyl,5),5-(丁烯-3-炔-1)-联噻吩[5-(but-3-en-1-ynyl)-2,2'-bithiophene,6],木栓酮(fredelin,7),卡多帕亭(cardopatine,8),异卡多帕亭(isocardopatine,9),羽扇豆醇(lupeol,10),5-乙酰基-2,2'-联噻吩(5-acetyl-2,2'-bithiophene,11),4,6,8(14),22(E)-四烯-3-酮-麦角甾[ergosta-4,6,8(14),22(E)-tetraen-3-one,12],丁二酸(succinic acid,13),5-羟甲基糠醛(5-hydroxymethylfuraldehyde,14)。其中化合物7、12为首次从蓝刺头属植物中分离得到,也首次从该植物的地上部分分离得到噻吩类成分。
利用人类慢性骨髓性白血病K562细胞模型,以细胞周期抑制和细胞凋亡诱导活性为筛选指标,对蓝刺头地上部分95%乙醇提取物各萃取部分及70%乙醇提取物进行活性筛选,确定其抗癌活性成分集中于95%乙醇提取物的石油醚萃取部分及氯仿萃取部分。
采用MTT法和SRB法,对分离得到的噻吩类成分的体外肿瘤抑制活性进行了初步研究。研究发现测试化合物均显示出光敏活性,对试验细胞系具有明显的依赖于长波紫外光的细胞毒作用。
In the dissertation,2 kinds of medicinal plants were studied.
1.Helichrysum arenarium(L.) distributed mainly in Xinjiang Uygur Autonomous Region of China,Mongolia,Europe and Russia.It is a medicinal plant which has been long known in European traditional medicine as a cholagogue,choleretic, hepatoprotective and detoxifying agent.It also has antioxidant,and anti-bacterial activities on the basis of modern pharmacological reasearch,and previous phytochemical study on this plant revealed the presence of flavonoids and phenolic acids.
From the ethanol extracts of the whole herbal of H.arenarium,41 compounds were isolated by means of solvent partition,repeated column chromatography on silica gel,polyamide,Sephadex LH-20,pre-HPLC,and recrystallization.On the basis of analysis of NMR,MS data,measurement of physico-chemical characters and chemical methods,their structures were identified as:apigenin(1), apigenin-7-O-β-D-glucopyranoside(2),kaempferol(3), kaempferol-3-O-β-D-glucopyranoside(4),kaempferol-7-O-β-D-glucopyranoside(5), kaempferol-7-O-α-L-rhamnoside(6),luteolin(7),luteolin-7-O-β-D-glucopyranoside(8), quercetin(9),quercitrin(10),rutin(11),naringenin(12),5-hydroxy-4'-methoxyisoflavone(13),5-hydroxy- 4'-methoxyisoflavone-7-O-β-D-glucopyranoside (14),6,8-dimethoxy-3,5,7-trihydroxy-flavone(15),3,5-dihydroxy-6,7, 8-trimethoxyflavone(16),5,6,4'-trihydroxyflavone-7-O-β-D-glucopyranoside(17),5, 4'-dihydroxy-6,7,3',5'-tetramethoxyflavone(18),5,7,4'-trihydroxy-8-methoxyflavone (19),6,7-dimethoxy-4-hydroxy -1-naphthoic acid(20),caffeic acid(21),methyl caffeate (22),protocatechuic acid(23),p-hydroxybenzoic acid(24),arbutin(25),isovanillic acid (26),gallic acid(27),quininic acid(28),methyl quinic ester(29),caffeotannic acid(30), 1,3- O-dicaffeoylquinic acid(31), (Z)-5-hydroxy-7-methoxy-4-[3-methyl-4-(O-β-D-xylopyranosyl)but-2-enyl]isobenzofur an-l(3H)-one(32),5-hydroxy-7-O-β-D-glucopyranosyl-isobenzofuran-l(3H)-one(33), scopoletin(34),6-(4'-hydroxy-trans-styryl)-4-methoxy-2-pyrone(35),syllo-insitol(36), betulic acid(37),oleanolic acid(38),ursolic acid(39),β-sitosterol(40),daucosterol (41).Among them,compounds 20,and 32 were new compounds;compounds 6,13,14, 17,18,26,29,33,and 37 were firstly isolated from the Helichrysum genus.
The extracts and some compounds from H.arenarium were tested for anti-bacterial, anti-tumor and anti-inflammatory activities.
On the basis of references,a review was given on the structural modification of natural bioactive products.
2.Echinops latifolius Tausch is a traditional Chinese medicine,which widely distributed in the northern part of China.The roots of E.latifolius have been used to clear heat,expel miasma and stimulate milk section for a long history.It has been recorded in Chinese Pharmacopoeia(1995 Edition) as one of the sources for Yuzhou Loulu.Recent researches indicated that Yuzhou Loulu had the effects of anti-tumor, anti-virus,anti-fungal,anti-inflammatory and hepatoprotective effects.
By means of column chromatography,preparative thin-layer chromatography and Sephadex LH-20,14 compounds were isolated from the aerial part of E.latifolius.On the basis of physico-chemical properties and spectroscopic analysis,they were identified as:β-sitosterol(1),echinopsine(2),taraxerol acetate(3),daucosterol(4),α-terthienyl(5),5 -(but-3-en-1-ynyl)-2,2'-bithiophene(6),fredelin(7),cardopatine(8), isocardopatine(9),lupeol(10),5-acetyl-2,2'-bithiophene(11),ergosta-4,6,8(14),22 (E) -tetraen-3-one(12),succinic acid(13),5-hydroxymethylfuraldehyde(14).
Among them,compounds 7 and 12 were isolated from the Echinops genus for the first time,the thiophene derivates were obtained from the aerial part of the plant for the first time also.
The extracts of the aerial part of E.latifolius were bioassied for their cell cycle inhibitory and apoptosis inducing activities using K562 cells.The anti-tumor parts were found in the petroleum ester extract and the chloroform extract.
By MTT and SRB methods,the cytotoxic activities of the thiophenes isolated were assayed in vitro.All the compounds showed significant phototoxic activities against tumor cell lines,dependent on the long wavelength ultraviolet(UVA).
引文
[1]E.Czinner,L.Kursiinszki,D.Baumann.Phytochemical study of phenolic compounds from Helichrysi flos by LC-DAD-MS[J].Proceedings of the Phytochemicai Society of Europe,2002,47(Natural Products in the New Millennium:Prospects and Industrial Application):99-109.
[2]E.Czinner,K.Hagymasi,A.Blazovics.In vitro antioxidant properties of Helichrysum arenarium(L.) Moench[J].Journal of Ethnopharmacol,2000,73(3):437-443.
[3]U.Oezgen,A.Mavi,Z.Terzi.Antioxidant activities and total phenolic compounds amount of some Asteraceae species[J].Turkish Journal of Pharmaceutical Sciences,2004,1(3):203-216.
[4]A.Rancic,M.Sokovic,J.Vukojevic.Chemical composition and antimicrobial activities of essential oils of Myrrhis odorata(L.) Scop,Hypericum perforatum L and Helichrysum arenarium(L.) Moench[J].Journal of Essential Oil Research,2005,17(3):341-345.
[5]L.P.Smirnova,L.N.Pervykh.Quantitative determination of total flavonoids in flowers of Helichrysum arenarium[J].Khimiko-Farmatsevticheskii Zhurnal,1998,32(6):35-38.
[6]A.H.Mericli,B.Damadyan,B.Cubukcu.Flavonoids of Turkish Helichrysum arenarium(L.)Moench(Asteraceae)[J].Scientia Pharmaceutica,1986,54(4):363-5.
[7]E.Dombrowicz,A.L.Swiatek,W.Kopycki.Phenolic acids in Inflorescentia Helichrysi and Herba Hieracii pilosellae[J].Pharmazie,1992,47(6):469-70.
[8]A.I.Derkach,N.F.Komissarenko,V.T.Chernobai.Coumarins from inflorescences of Calendula officinalis and Helichrysum arenarium[J].Khimiya Prirodnykh Soedinenii,1986,(6):777.
[9]J.Vrkoc,K.Ubik,P.Sedmera.Phenolic extractives from the achenes of Helichrysum arenarium [J].Phytochemistry,1973,12(8):2062.
[10]J.Vrkoc,C.Akad,V.Prague.Plant substances.XIV.Sitosterol glucutonide[J].Collection of Czechoslovak Chemical Communications,1962,27:1345-6.
[11]K.G.Bel'tyukova.Plant antibiotic,arenarin[J].Mikrobiologichnii Zhurnal,1968,30(5):390-398.
[12]B.Tepe,M.Sokmen,H.Askin Akpulat.In vitro antioxidant activities of the methanol extracts of four Helichrysum species from Turkey[J].Food Chemistry,2005,90(4):685-689.
[13]Z.Sroka B,L.Kuta,W.Cisowski.Antiradical activity of hydrolyzed and non-hydrolyzed extracts from Helichrysi inflorescentia and its phenolic contents[J].Zeitschrift fuer Naturforschung,C:Journal of Biosciences,2004,59(5/6):363-367.
[14]S.M.Drogovoz,L.I.Filippova.Pharmacodynamics of flamin[J].Vrachebnoe Delo,1984,(11):99-101.
[1]Y.H.Gong.~(13)C NMR chemical shift of natural organic compounds,p 335,Yunnan Science and Technology Press,Yunnan(1986).
[2]任玉琳,杨峻山.西藏雪莲花化学成分的研究Ⅱ[J].中国药学杂志,2001,36(9):590-593.
[3]许婧,李铣,张鹏,等.金刚藤的黄酮类化学成分[J].沈阳药科大学学报,2004,21(6):424-425.
[4]EI Sherbeiny A.E.A.,El Sissi H.I.,Nawwar M.A.M.,et aL.The flavonoids of the seeds of Lygos raetam.PLanta Medica,1978,34(3):335-336.
[5]李宁,李铣,杨世林,等.过山蕨总黄酮的化学成分研究[J].沈阳药科大学学报,2004,21(2):105-108.
[6]汤芳萍,吴翠芳.山葡萄化学成分的研究[J].湖南中医学院学报,2003,23(4):21-22
[7]杨爱梅,刘霞,鲁润华,等.藏药川西小黄菊中黄酮类成分的分离与结构鉴定[J].中草药,2006,37(1):25-27.
[8]Cross G.A.,Meiei B.,Sticher O.Complex flavonol glycosides from the leaves of Ginkgo biLoba.Phytochemistry,1992,21(4):1391-1394.
[9]蒋受军,魏峰,鲁静,等.小野芝麻的化学成分研究[J].中国药科大学学报,2002,33(6):487-488.
[10]魏均娴,左群英,朱焰.普洱茶籽的化学成分研究[J].中国中药杂志,1997,22(4):228-230.
[11]谭永霞,孙玉华,陈若芸.鹰嘴豆化学成分研究[J].中国中药杂志,2007,32(16):1650-1652.
[12]王景华,王亚琳,楼凤昌.槐树种子的化学成分研究[J].中国药科大学学报,2001,32(6):471-473.
[13]H.Tokunaru,K.Takeshi,K.Yasuhiko.Studies of the selective O-alkylation and dealkylation of flavonoids.XXI.Aconvenient method for synthesizing 3,5,7-trihy droxy-6,8-dimethoxy flavones and 5,7-dihy droxy-3,6,8-trimethoxy flavones[J].Bulletin of the Chemical Society of Japan,1996,69(4):1033-41.
[14]Van Puyvelde,Luc;De Kimpe,Norbert;Costa,Jean;Munyjabo,Viateur;Nyirankuliza,Speciosa;Hakizamungu,Etienne;Schamp,Niceas.Isolation of flavonoids and a chalcone from Helichrysum odoratissimum and synthesis of Helichrysetin[J].Journal of Natural Products,1989,52(3):629-633.
[15]张永红,汪涛,芦志刚,等.鼬瓣花化学成分研究[J].中国中药杂志,2002,27(3):206-208
[16]Nagao,Tsuneatsu;Abe,Fumiko;Kinjo,Junei;Okabe,Hikaru.Antiproliferative constituents in plants 10.Flavones from the leaves of Lantana montevidensis Briq.And consideration of structure-activity relationship.Biological & Pharmaceutical Bulletin,2002,25(7):875-879.
[17]王红燕,肖丽和,刘丽,等.粘毛黄芩根的化学成分研究[J].沈阳药科大学学报,2003,20(5):339-342.
[18]凌云,鲍燕燕,张永林,等.兴安蒲公英的化学成分研究.中草药,2000,31(1):10-11.
[19]王代岱,米彩峰.西芎藁本的化学成分研究.西北药学杂志,1993,8(1):19-21.
[20]李勇军,何迅,刘丽娜,等.荭草化学成分的研究.中国中药杂志,2005,30(6):444-446.
[21]李宁,李铣,杨世林.过山蕨中有机酸类化学成分.沈阳药科大学学报,2006,23(7):427-429.
[22]Zhong X.N.,Otsuka H.,Ide T.,et al.Hydroquinone glycosides from leaves of Myrsine seguinii.Phytochemistry,1998,49(7):2149-2153.
[23]解军波,李萍.四季青酚酸类化学成分研究.中国药科大学学报,2002,33(1):76-77.
[24]Nishimum H.,Nonaka G.I.,Itsuo.Seven quinic acid gallates from quercus stenophylla[J].Phytochemistry,1984,23(11):2621-2623.
[25]Takayama H.,Ohmori O.,Sakai M.,et al.Isolation,partial synthesis and stereochemical study of 10-hydroxystrictosamide,a constituent of Nauclea orientalis in Thailand[J].Heterocycles,1998,49:49-52.
[26]刘延泽,王彩芳,韩金斌,等.柳兰化学成分研究II[J].鞣质及多元酚类化合物[J].中草药,2003,34(11):967-969.
[27]Dini,I.,Tenore,G.C.,Dini,A.New Polyphenol Derivative in Ipomoea batatas Tubers and Its Antioxidant Activity[J].Journal of Agricultural and Food Chemistry,2006,54(23):8733-8737.
[28]黄莹,张德志.细叶杜香化学成分的研究(II)[J].广东药学院学报,2008,24(1):33-35.
[29]Wang A.X.,Zhang Q.,Jia Z.J.A new furobenzopyranone and other constituents from Anaphalis lactea[J].Pharmazie,2004,59(10):807-811.
[30]Braca,A.,Morelli,I.,Mendez,J.,et al.Antimicrobial triterpenoids from Licania heteromorpha[J].Planta Medica,2000,66(8):768-769.
[31]赵江霞,马龙,堵年生,等.新疆和田红葡萄果皮化学成分的研究.新疆医科大学学报,2001,24(3):189-191.
[32]王晓明,谢从炳,王磊.长冠鼠尾草的化学成分研究[J].华中科技大学学报(医学版),2002,31(6):254-255.
[33]杜树山,徐艳春,魏璐雪.毛蕊老鹳草水溶性化学成分研究[J].中草药,2003,34(6):501-502.
[1]E.Czinner,L.Kursiinszki,D.Baumann.Phytochemical study of phenolic compounds from Helichrysi flos by LC-DAD-MS[J].Proceedings of the Phytochemical Society of Europe,2002,47(Natural Products in the New Millennium:Prospects and Industrial Application):99-109.
[2]E.Czinner,K.Hagymasi,A.Blazovics.In vitro antioxidant properties of Helichrysum arenarium(L.) Moench[J].Journal of Ethnopharmacol,2000,73(3):437-443.
[3]U.Oezgen,A.Mavi,Z.Terzi.Antioxidant activities and total phenolic compounds amount of some Asteraceae species[J].Turkish Journal of Pharmaceutical Sciences,2004,1(3):203-216.
[4]A.Rancic,M.Sokovic,J.Vukojevic.Chemical composition and antimicrobial activities of essential oils of Myrrhis odorata(L.) Scop,Hypericum perforatum L and Helichrysum arenarium(L.)Moench[J].Journal of Essential Oil Research,2005,17(3):341-345.
[1]Wani,Mansukhlal C.;Taylor,Harold Lawrence;Wall,Monroe E.;et al.Plant antitumor agents.VI.Isolation and structure of taxol,a novel antileukemic and antitumor agent from Taxus brevifolia[J].Journal of the American Chemical Society,1971,93(9):2325-2327.
[2]李媛,李振宇.天然抗癌药物-紫杉醇[J].中山大学研究生学刊(自然科学、医学版),2006,27(4):58-62.
[3]Nicolaou K.C.,Yang Z.,Liu J.J.,et al.Total synthesis of taxol[J].Nature,1994,367(64): 630-634.
[4]岳琴,方起程,梁晓天.紫杉醇的半合成[J].药学学报,1996,31(12):911-917.
[5]Shiina,Isamu;Saitoh,Katsuyuki;Frechard-Ortuno,Isabelle;Mukaiyama,Teruaki.Total asymmetric synthesis of taxol by dehydration condensation between 7-TES baccatin III and protected N-benzoylphenylisoserines prepared by enantioselective aldol reaction[J].Chemistry Letters,1998,27(1):3-4.
[6]李燕,王永华,房华,等.紫杉醇类衍生物的定量结构-抗癌活性关系研究进展[J].中国药理学通报,2008,24(3):288-293.
[7]方起程.天然化合物结构修饰是创制新药的重要途径[J].中国新药杂志,2006,15(16):1321-1324.
[8]Gueritte,Francoise.General and recent aspects of the chemistry and structure-activity relationships of taxoids[J].Current Pharmaceutical Design,2001,7(12):1229-1249
[9]齐传民,王蕴峰,王力元,等.四步纯化法合成多西紫杉醇的工艺研究[J].化工科技,2003,11(2):1-6.
[10]Powell RG,Weisleder D,Smith CR,et al.Structure of cephalotaxine and related alkaloids[J].Tetrahedron Letters,1969,10(46):4081-4084.
[11]韩锐.肿瘤化学预防及药物治疗[M].北京:北京医科大学中国协和医科大学联合出版社.1991.212-315.
[12]李述文,孙菡丽,卢秀静,等.三尖杉碱酯类化合物的合成及其抗肿瘤活性[J].药学学报.1981,16(11):821-827.
[13]王永铿,李裕林,潘鑫复,等.高三尖杉酯碱的合成及其差向异构体的分离鉴定[J].化学学报.1985,43(2):161-167.
[14]黄文魁,李裕林,潘鑫复,等.脱氧粗榧酯碱的合成[J].兰州大学学报(自然科学版),1974,5:74-77.
[15]潘鑫复,李裕林,李绍白,等.异三尖杉酯碱的合成[J].科学通报.1982,27(17):1048.
[16]王永铿,穆启运,李裕林,等.高脱氧三尖杉酯碱的合成及其差向异构体的分离鉴定[J].化学学报,1983,4 1(7):648-653.
[17]李绍白,崔育新,李裕林,等.高异三尖杉酯碱的合成及其立体异构体的分离鉴定[J].化学学报.1987,45(7):687-691.
[18]王定志,马广恩,徐任生.三尖杉属植物中生物碱的研究-Ⅷ.二种新的抗癌三尖杉酯碱生物碱的结构和半合成[J].药学学报.1992,27(3):173-177.
[19]钟三保,刘维勤,李仁利,等.三尖杉酯类生物碱的半合成及结构与抗肿瘤活性的关系[J].药学学报.1994,29(1):33-38.
[20]李占荣,韩锐.新抗肿瘤药——三尖杉酯碱及高三尖杉酯碱研究进展[J].中草药,1986,17(3):39-45.
[21]张强,闻韧,Henin J,等.三尖杉碱吲哚类似物的全合成[J].上海医科大学学报,2000,27 (3):157-162.
[22]叶仙蓉,吴克美.三尖杉碱和桥氧三尖杉碱衍生物的合成及抗肿瘤活性.药学学报.2003.38(12):919-923.
[23]叶仙蓉,柴永海,李行南,等.三尖杉酯碱衍生物的合成及抗肿瘤活性.药学学报.2004,39(6):429-433.
[24]刘纪云,张宝殉,李瑞禧.肿瘤化学治疗的研究——斑蝥素衍生物的合成[J].药学学报,1980,15(5):271-277.
[25]刘纪云,张保珣,孙家莉.肿瘤化学治疗的研究——II.斑蝥素衍生物和类似物的合成[J].药学学报,1983,18(10):752-759.
[26]王广生.斑蝥素水解及去甲对其泌尿系统刺激的缓解[J].药学通报,1983,18(7):18-19.
[27]田少雷,赵树纬,朱爱堂,等.抗肿瘤药物研究I:去甲斑蝥素氨基酸衍生物的合成与抗癌活性[J].药学学报,1 993,28(11):870-875.
[28]孙铁民,沈建民.呋喃乙醇胺类和苯并呋喃乙醇胺类化合物的合成[J].中国药物化学杂志,1993,3(3):157-162.
[29]方茵,田少雷,李克庆,等.抗肿瘤药物研究II:去甲斑蝥素去氧脱氢类似物的合成与抗癌活性[J].药学学报,1993,28(12):931-935.
[30]王莉莉,周应军.抗癌物质鬼臼毒素及其衍生物研究进展[J].国外医药·植物药分册,2006,21(1):6-9.
[31]Stuehelin,H.F.,Von-Wartburg A.The chemical and biological route from podophyllotoxin glucoside to etoposide:Ninth Cain Memorial Award Lecture[J].Cancer Research,1991,51(1):5-15.
[32]Ravnihar B,MacMahon B,Lindtner J.Epidemioiogic features of breast cancer in Slovenia,1965-1967[J].European Journal of Cancer,1971,7(4):295-306.
[33]Staehelin,H.Activity of a new glycosidic lignan derivative(VP 16-213) related to podophyllotoxin in experimental tumors[J].European Journal of Cancer,1973,9(3):215-221.
[34]Mistry P.,Kelland L.R.,Abel G.,et al.The relationships between glutathione,glutathione-S-transferase and cytotoxicity of platinum drugs and melphalan in eight human ovarian carcinoma cell lines[J].British Journal of Cancer,1991,64(2):215-220.
[35]Doyle T.W.,Vyas D.M.Second generation analogs of etoposide and mitomycin C[J].Cancer Treatment Review.,1990,17(2-3):127-131.
[36]US Patent 4,916,217,1990.
[37]Leeson P.A.,Castaner J.TOP-53.Antineoplastic podophyllotoxin DNA topoisomerase II inhibitor[J].Drugs of the Future,1996,21(11):1136-1139.
[38]Wall M.E.,Wani M.C.,Cook C.E.,et al.Plant antitumor agents.I.Isolation and structure of camtothecin,a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata[J].Journal of the American Chemical Society,1966,88(16):3888-3890.
[39]Wani M.C.,Wall M.E.Plant antitumor agents.II.Structure of two new alkaloids from Camptotheca acuminata[J].Journal of Organic Chemistry,1969,34(5):1364-1367.
[40]金学平,金学兰.天然抗肿瘤药物羟基喜树碱的制备方法研究概况[J].中国药业,2006,15(19):63-64.
[41]陈迪华,李荣芳,叶鸿盘.中药青黛抗白血病成分-靛玉红的合成[J].中草药通讯,1979,10(3):7-9.
[42]吴克美,张曼云,方正,等.抗白血病药物靛玉红的N_(1')-取代物的合成[J].药学学报,1984,19(7):513-518.
[43]吴克美,张曼云,方正,等.抗白血病药物靛玉红以及靛蓝和异靛蓝衍生物的合成[J].药学学报,1985,20(11):821-826.
[44]潘百川,张红,潘纯英,等.美登素全合成的研究[J].化学学报,1980,38(5):502-507.
[45]周启霆,白东鲁,潘百川,等.美登醇的全合成[J].科学通报,1985,(19):1556-1559.
[46]陈求浩,庞贻慧,孙秀英.五种预测药物有效期方法的通用计算机程序[J].医药工业,1986,17(7):11-15.
[47]楼凤昌,丁林生,马琴玉,等.具有抗肿瘤作用的天然化合物机器构效关系[J].南京药学院学报,1986,17(2):152-159.
[48]赵龙铉,刘宁宁,裴晓娟,等.熊果酸和齐墩果酸衍生物的合成与表征[J].辽宁师范大学学报(自然科学版),2007,30(4):476-479.
[49]陈莉,孔祥文,张奕华.齐墩果酸酯的合成研究(I)[J].中草药,2003,34(12):1080-1081.
[50]陈莉,张奕华,毕小玲,等.齐墩果酸酯的合成研究(II)[J].中南药学,2006,4(6):416-418.
[51]刘明生,谷黎红,陈英杰,等.齐墩果酸磷酸酯单钠的合成[J].中国药物化学杂志,1993,3(1):42-43.
[52]Jeong H J,Chai H B,Park S Y,et al.Preparation of amino acid conjugates of betulinic acid with activity against human melanoma[J].Bioorganic and Medicinal Chemistry Letters,1999,9(8):1201-1204.
[53]孙华,胡春,方唯硕.3-氧代齐墩果酸氨基酸偶联物的合成、水溶性的测定及抗肿瘤活性研究[J].中国药物化学杂志,2008,18(1):11-15.
[54]Hostettmann K.,Marston A.Saponins,Cambridge university press,1995.
[55]刘美正,郭忠武,惠永正,皂苷研究新进展[J].天然产物研究与开发,1997,9,81-85.
[56]Kim H.Y.,Kim K.Protective Effect of Ginseng on Cytokine-Induced Apoptosis in Pancreatic-Cells[J].Journal of Agricultural and Food Chemistry,2007,55(8):2816-2823.
[57]Hasegawa H.,Sung J.H.,Matsumiya S.,et al.Reversal of daunomycin and vinblastine resistance in multidrug-resistant P388 Leukemia in vitro through enhanced cytotoxieity by triterpenoids[J].Planta Medica,1995,61(5):409-411.
[58]Kim Y.S.,Kim D.S.,Kim S.I.Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytes:modulation of protein kinase C isoforms during differentiation by ginsenoside Rh2[J].International Journal of Biochemistry & Cell Biology,1998,30(3):327-338.
[59]Lee Y.N.,Lee H.Y.,Chung H.Y.,et al.In vitro induction of differentiation by ginsenosides in F9 teratocarcinoma cells[J].European Journal of Cancer,Part A,1996,32A(8):1420-1428.
[60]李平亚,刘金平,卢丹,等.抗癌药物“20(S)-人参皂苷 Rg3 注射液的研制.科技成果,2004.
[61]小岛田肃夫.日本临床,2003,19(3):282-286.
[62]王红燕,徐绥褚,陈英杰.人参化学成分研究的新进展[J].中国药物化学杂志,1992,2(1):65-72.
[63]Cha B.C.,Lee S.G Preparation of ginsenoside-Rh2 from dammarane saponins of Panax ginseng leaves[J].Yakhak Hoechi,1994,3 8(4):425-429.
[64]刘惟,陈英杰,刘明生.人参皂苷 Rh2 的半合成[J],沈阳药学院学报,1988,5(1):1-15.
[65]金凤燮,鱼红闪,赵立亚.酶法生产稀有人参皂苷及其产物成分的分析[J].大连轻工学院学报,2002,21(3):112-115.
[66]刘惟瑳,陈英杰,刘明生,等.人参皂苷 Rh'2 的半合成[J].沈阳药学院学报,1988,5(1):14-15.
[67]吴秀丽,王艳,赵文倩,等.一种真菌对人参皂苷 Rg_3 的转化[J].微生物学报,200848(9):1181-1185.
[68]马成俊.半合成稀有人参皂苷及抗肿瘤构效关系的研究[J].中国科学院研究生院,博士学位论文
[69]周伟,周佩.稀有人参皂苷 compound K 研究进展[J].药学学报,2007,42(9):917-923.
[70]姜彬慧,韩颖,赵余庆,等.酶转化三七叶总皂苷制备人参皂苷 C-K 的工艺优化[J].中草药,2004,35(9):986-989.
[71]Kim,B.H.,Lee,S.Y.,Cho,H.J.,et al.Biotransformation of Korean Panax ginseng by pectinex.Biological & Pharmaceutical Bulletin,2006,29(12):2472-2478.
[72]Hasegawa,H.,Sung,J.H.,Matsumiya,S.,et al.Main ginseng saponin metabolites formed by intestinal bacteria.Planta Medica,1996,62(5):453-457.
[73]Suda,K.,Murakami,K.,Murata,J.,et al.An intestinal bacterial metabolite(M1) of ginseng protopanaxadiol saponins inhibits tumor-induced neovascularization[J].Wakan Iyakugaku Zasshi,2000,17(4):144-150.
[74]Hasegawa,H.;Lee,K.S.;Nagaoka,T.,et al.Pharmacokinetics of ginsenoside deglycosylated by intestinal bacteria and its transformation to biologically active fatty acid esters[J].Biological &Pharmaceutical Bulletin,2000,23(3):298-304.
[75]李娜,孙印石,孙彦君,等.人参皂苷次生代谢产物的研究[J].吉林中医药,2008,28(7):523-525.
[76]曾飒,关永源,刘德育,等.人参皂苷 RdC-12 差向异构体的合成及其对大鼠主动脉环收缩反应的影响[J].中国药理学通报,2003,19(3):282-286.
[77]于荣敏,宋永波,张辉,等.西洋参冠瘿组织培养及其人参皂苷 Re 和人参皂苷 Rgl 的产生[J].生物工程学报,2003,19(3):372-375.
[78]Dong,A.;Cui,Y.;Guo,H.Z.et al.Microbiological transformation of ginsenoside Rgl[J].Journal of Chinese Pharmaceutical Sciences,2001,10(3):115-118.
[79]吴秀丽,张怡轩,赵文倩,等.真菌 EST-I 及 EST-II 对人参皂苷 Rgl 定向转化为人参皂苷F1的研究[J].沈阳药科大学学报,2008,25(1):46-47,57,67.
[80]Hasegawa,H.;Benno,Y.Anticarcinogenesis in mice by ginseng-hydrolyzing colonic bacteria[J].Microbial Ecology in Health and Disease,2000,12(2):85-91.
[81]Hasegawa,H.;Sung,J.H.;Benno,Y.Role of human intestinal Prevotella oris in hydrolyzing ginseng saponins[J].Planta Medica,1997,63(5):436-440.
[82]Hasegawa,H.;Uchiyama,M.Antimetastatic efficacy of orally administered ginsenoside Rbl in dependence on intestinal bacterial hydrolyzing potential and significance of treatment with an active bacterial metabolite[J].Planta Medica,1998,64(8):696-700.
[83]Matsuda H.,Namba K.,Fukuda S.et al Pharmacological study on Panax ginseng C.A.Meyer.IV.Effects of red ginseng on experimental disseminated intravascular coagulation.(3).Effect of ginsenoside-Ro on the blood coagulative and fibrinolytic system[J].Chemical & Pharmaceutical Bulletin,1986,34(5):2100-2104.
[84]Matsuda,H.;Samukawa,K.;Kubo,M.Pharmacological study on Panax ginseng C.A.Meyer.Part XI.Anti-inflammatory activity in ginsenoside Ro[J].Planta Medica,1990,56(1):19-23.
[85]Matsuda,H.;Samukawa,K.;Kubo,M.Anti-hepatitis activity of ginsenoside Ro[J].Planta Medica,1991,57(6):523-526.
[86]彭文杰.若干皂苷和黄酮苷的合成研究[M].中国科学院研究生院,博士学位论文
[87]孙彬贤,杨广孝,汪沁琳,等.人参毛状根合成人参皂苷培养条件的优化[J].中成药,2003,25(9):746-748.
[88]Xiao K.;Yi,Y.H.;Wang,Z.Z.,et al.A cytotoxic triterpene saponin from the root bark of Aralia dasyphylla[J].Journal of Natural Products,1999,62(7):1030-1032.
[98]Mimaki Y.,Yokosu K.A.,Sashida Y.,et al.Cytotoxic activities and structure cytotoxic relationships of steroidal saponins[J].Biological & Pharmaceutical Bulletin,2001,24(11):1286-1289.
[90]Nakamura T.,Komori C.,Ej Ima A.,et al.Cytotoxic activities of solanum steroidal glycosides[J].Biological & Pharmaceutical Bulletin,1996,19(4):564-566.
[91]Hu K.,Dong A.,Iwasaki S.,et al.Antineoplastic agents I.Three spirostanol glycosides from rhizomes of Dioscorea collettii var.hypoglauca[J].Planta Medica,1996,62(6):573-575.
[92]Chiang H.,Tseng T.H.,Kan W.,et al.Experimental antitumor agents from Solanum indicum L[J].Anticancer Research,1991,11(5):1911-1917.
[93]Deng S.J.,Yu B.,Hui Y.A facile synthetic approach to a group of structurally typical diosgenylsaponins[J].Tetrahedron Letters,1998,39(36):6511-6514.
[94]Li M.,Han X.,Yu B.Synthesis of monomethylated dioscin derivatives and their antitumor activities [J].Carbohydrate Research,2003,338 (2):117-121.
[95]Zhu S.L.,Zhang Y.C.,Yu B.,et al.Synthesis and cytotoxicities of dioscin derivatives with decorated chacotriosyl residues [J].Bioorganic and Medicinal Chemistry Letters,2006,16 (21):5629-5632.
[96]Zhang,Y.C.,Li,Y.G.,Guo,T.T.,et al.Syntheses of chlorogenin 6α-O-acyl-3-O-β-chacotriosides and their antitumor activities [J].Carbohydrate Research,2005,340 (8):1453-1459.
[97]Mimaki Y.,Kanmoto T.,Nishino A.,et al.Steroidal saponins from Hosta longipes and their inhibitory activity on tumour promoter-induced phospholipid metabolism of HeLa cells [J].Phytochemistry,1996,42(4):1065-1070.
[98]Mimaki Y.,Kuroda M.,Sashida Y.,et al.Steroidal saponins from the rhizomes of Hostasieboldii and their cytostatic activity on HL-60 cells [J].Phytochemistry,1998,48 (8):1361-1369.
[99]3β-O-[2-O-(-L-rhamnopyranosyl)-β-D-galactopyranoside]and its congeners [J].Synthesis,2006,(5):775 - 782.
[100]Hernandez J.C.,L Eon F.,Quintana J.,et al.Icogenin,a new cytotoxic steroidal saponin isolated from Dracaena draco[J].Bioorganic and Medicinal Chemistry Letters,2004,12 (16):4423-4429.
[101]Hou S.J.,Xu P.,Zhou L.,et al.Synthesis and antitumor activity of icogenin and its analogue[J].Bioorganic and Medicinal Chemistry Letters,2006,16 (9):2454-2458.
[102]Hu K.,Dong A.J.,Yao X.S.,et al.A new pregnane glycoside from Dioscorea collettii var.hypoglauca[J].Journal of Natural Products,1999,62 (2):299-301.
[103]Cheng M.S.,Wang Q.L.,Yao X.S.,et al.Total synthesis of methyl protodioscin:A potent agent with antitumor activity [J].Journal of Organic Chemistry,2003,68 (9):3658-3662.
[104]Zhao D.M.,Liu Y.,Cheng M.S.,et al.Chemical intertransformations of diverse bisdesmosidic furostanol saponins [J].Chemistry Letters,2007,36 (2):214-216.
[105]Liu Y.,Zhao D.M.,Cheng M.S.,et al.Synthesis of bisdesmosidic kryptogenyl saponins using the random glycosylation strategy and evaluation of their antitumor activity [J].Bioorganic and Medicinal Chemistry Letters,2007,17 (1):156-160.
[106]Kubo S,Mimaki Y,Terao M,et al.Acylated cholestane glycosides from the bulbs of Ornithogalum saundersiae [J].Phytochemistry,1992,31 (11):3969-3973.
[107]Deng S.J.,Yu B.,Hui Y.,et al.First total synthesis of an exceptionally potent antitumor saponin OSW-1 [J].Journal of Organic Chemistry,1999,64 (1):202-208.
[108]Morzycki,Jacek W.,Wojtkielewicz,A.Synthesis of a cholestane glycoside OSW-1 with potent cytostatic activity [J].Carbohydrate Research,2002,337 (14):1269-1274.
[109]Yu W.,J In Z.Total synthesis of the anticancer natural product OSW-1 [J].Journal of the American Chemical Society,2002,124 (23):6576-6583.
[110]Mimaki Y.,Kuroda M.,Kameyama A.,et al.Cholestane glycosides with potent cytostatic activities on various tumor cells from Omithogalum saundersiae bulbs[J].Bioorganic and Medicinal Chemistry Letters,1997,7(5):633-636.
[111]Ma X.,Yu B.,Hui Y.,et al.Synthesis of glycosides bearing the disaccharide of OSW-1 or its 1→4-linked analogue and their antitumor activities[J].Carbohydrate Research,2000,329(3):495-505.
[112]Ma X.,Yu B.,Hui Y.,et al.Synthesis of steroidal glycosides bearing the disaccharide moiety of OSW-1 and their antitumor activities[J].Carbohydrate Research,2001,334(2):159-164.
[113]Ma X.,Yu B.,Hui Y.Synthesis of OSW-1 analogues and a dimer and their antitumor activities[J].Bioorganic and Medicinal Chemistry Letters,2001,11(16):2153-2156.
[114]Deng L.,Wu H.,Yu B.,et al.Synthesis of OSW-1 analogs with modified side chains and their antitumor activities[J].Bioorganic and Medicinal Chemistry Letters,2004,14(11):2781-2785.
[115]Shi B.,Wu H.,Yu B.,et al.Medicinal chemistry:23-Oxa-analogs of OSW-1:Efficient synthesis and extremely potent antitumor activity[J].Angewandte Chemie,International Edition,2004,43(33):4324-4327.
[116]Shi B.,Tang P.P.,Hu X.,et al.OSW saponins:Facile synthesis toward a new type of structures with potent antitumor activities[J].Journal of Organic Chemistry,2005,70(25):10354-10367.
[117]Tang P.P.,Mamdani F.,Yu B.,et al.Synthesis of OSW saponin analogs with modified sugar residues and their antiproliferative activities[J].Bioorg Med Chem Lett,2007,17(4):1003-1007.
[118]Morzycki J.W.,Woj Tkiel Ewicz A.Synthesis of a highly potent antitumor saponin OSW-1 and its analogues[J].Phytochemistry Reviews,2005,4(3):259-277.
[119]Mimaki Y.,Kuroda M.,Sashida Y.,et al.Candicanoside A,a novel cytotoxic rearranged cholestaneglycoside from Galtonia candicans[J].Helvetica Chimica Acta,2000,83(10):2698-2704.
[120]Tang P.P.,Yu B.Total synthesis of candicanoside A,a potent antitumor saponin with a rearranged steroid side chain[J].Angewandte Chemie International Edition,2007,46(14):2527-2530.
[121]Schroeter,G.;Lichtenstadt,L.;Irineu,D.Constitution of substances from guaiacurn resin[J].Berichte der Deutschen Chemischen Gesellschaft,1918,51:1587-1613.
[122]Hwu,J.R.;Tseng,W.N.;Gnabre,J.et al.Antiviral Activities of Methylated Nordihydroguaiaretic Acids.1.Synthesis,Structure Identification,and Inhibition of Tat-Regulated HIV Transactivation[J].Journal of Medicinal Chemistry,1998,41(16):2994-3000.
[123]Ezberci,F.;Tekin,E.;Onuk,E.Protective effect of a lipoxygenase inhibitor,nordihydroguaretic acid,on the ileal motor disturbances induced by Serratia marcescens endotoxin in rats[J].Surgery Today,2001,31(6):497-501.
[124]Chen,H.S.;Teng,L.;Li,J.N.et al.Antiviral Activities of Methylated Nordihydroguaiaretic Acids.2.Targeting Herpes Simplex Virus Replication by the Mutation Insensitive Transcription Inhibitor Tetra-O-methyl-NDGA[J].Journal of Medicinal Chemistry,1998,41(16):3001-3007.
[125]Whitman,S.;Gezginci,M.;Timmermann,B.N.et al.Structure-activity relationship studies of nordihydroguaiaretic acid inhibitors toward soybean,12-human,and 15-human lipoxygenase[J].Journal of Medicinal Chemistry,2002,45(12):2659-2661.
[126]Barnaby,J.W.;Styles,A.R.;Cockerell,C.J.Actinic keratoses.Differential diagnosis and treatment[J].Drugs & aging,1997,11(3):186-205.
[127]Sahu,S.C.;Ruggles,D.I.;O'Donnell,M.W.Prooxidant activity and toxicity of nordihydroguaiaretic acid in clone-9 rat hepatocyte cultures[J].Food and Chemical Toxicology,2006,44(10):1751-1757.
[128]Mak,D.H.;Schober,W.D.;Chen,W.J.et al.Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of leukemia cells independent of Cdc 2 and survivin[J].Leukemia & Lymphoma,2007,48(4):774-785.
[129]Blecha,J.E.;Anderson,M.O.;Chow,J.M.,et al.Inhibition of IGF-lR and lipoxygenase by nordihydroguaiaretic acid(NDGA) analogs[J].Bioorganic & Medicinal Chemistry Letters,2007,17,4026-4029.
[130]Shimomura,H.;Sashida,Y.;Oohara,M.Lignans from Machilus thunbergii[J].Phytochemistry,1987,26,1513-1515.
[131]Perry,C.W.;Kalnins,M.V.;Deitcher,K.H.Synthesis of lignans[J].Journal of Organic Chemistry,1972,37(26):4371-4376.
[132]吴安心,赵玉瑞,陈宁,等.去甲二氢愈创木酸的全合成[J].药学学报,1997,32(4):39-42.
[133]Gezginci,M.H.;Timmermann,B.N.A short synthetic route to nordihydroguaiaretic acid (NDGA) and its stereoisomer using Ti-induced carbonyl-coupling reaction[J].Tetrahedron Letters.2001,42,6083-6085.
[134]潘鑫复,陈小川.木质素类化合物的全合成研究[J].有机化学,2001,21(11):1060-1064.
[135]夏亚穆,王琦,王一宁.meso-去甲二氢愈创木酸和 Machilin A 的合成[J].有机化学,2008,28(6):1040-1043.
[136]Nemethy E.K.,Lago R.,Hawkins D.,et al.Lignans of Myristica Otoba[J].Phytochemistry,1986,25(4):956-960.
[137]MacRae,W.D.,Towers,G.H.N.Biological activities of lignans[J].Phytochemistry,1984,23(6):1207-1220.
[138]刘嘉森,黄梅芬.华中五味子的研究[J].化学学报,1984,42(3):264-270.
[139]Gunasekaran,A.,Balasubramanian,K.Syntheses of(±)-deoxyschizandrin and the lignan,1,4-bis(3,4-dimethoxyphenyl)-2,3- dimethylbutane[J].Indian Journal of Chemistry,Section B:Organic Chemistry Including Medicinal Chemistry,1988,27B(4):308-310.
[140]吴安心,潘鑫复,杨维东,等.1,4-二(3,4-二甲氧基苯基)-2,3-二甲基丁烷的全合成[J].中国药物化学杂志,1997,7(2):28-31.
[141]Sydiskis,R.J.;Dwen,D.G.;Lohr,J.L.et al.Inactivation of enveloped viruses by anthraquinones extracted from plants[J].Antimicrobial Agents and Chemotherapy,1991,35(12):2463-2466.
[142]Anderson,D.O.;Weber,N.D.;Wood,S,G.et al.In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives[J].Antiviral Research,1991,16(2):185-196.
[143]Schinazi,R.F.;Chung,K.;Chu,J.;et al.Anthraquinones as a new class of antiviral agents against human immunodeficiency virus[J].Antiviral Research,1990,13(5):265-272.
[144]陈琼华,郑武飞,苏学良,等.中药大黄的综合研究I.大黄中蒽醌衍生物抗菌效价的研究[J].药学学报,1962,9(12),,757-762.
[145]陈琼华,李电东,苏学良,等.中药大黄的综合研究[J].生物化学与生物物理学报,1963,3(4):426-433.
[146]Graham,J.A.,Bruce,F.C.,Bruce,C.B.,et al.Potential antitumor agents.Part 43.Synthesis and biological activity of dibasic 9-aminoacridine-4-carboxamides,a new class of antitumor agent[J].Journal of Medicinal Chemistry,1984,27(11):1481-5.
[147]陆豫,黄志纾,谭嘉恒,等.大黄素衍生物的合成及细胞毒性研究[J].有机化学,2005,25(8):944-948.
[148]张韶湘,邹澄,赵庆,等.小檗碱衍生物的合成及药理活性研究[J].中国民族民间医药杂志,2007,3:167-172.
[149]东北制药总厂.医药工业,1975,(4):12.
[150]Iwasa K,KamigauchiM,SugiuraM,et al.Antimicrobialactivity of some 13-alkyl substituted p rotoberberinium salts[J].Planta Medica,1997,63:196-198.
[151]Iwasa K,Nanba H,Lee DU,et al.Structure activity relationship s of p rotoberberines having antimicrobial activity[J].Planta Medica,1998,64:748-751.
[152]Iwasa K,Lee DU,Kang SI,et al.Antimicrobial activity of 8-alkayl and 8-phenyl-substituted berberines and their 12-bromo derivatives[J].Journal of Natural Products,1998,61:1150-1153.
[153]Park KD,Lee JH,Kim SH,et al.Synthesis of 13-(substituted benzyl ) berberine and berberrubine derivatives as antifungal agents[J].Bioorganic and Medicinal Chemistry Letters,2006,16:3913-3916.
[154]Yang Y,Ye XL,L i XG.Synthesis and antimicrobial activity of 8-alkylberberine derivatives with a long aliphatic chain[J].Planta Medica,2007,73:602-604.
[155]Hong SW,Kim SH,Jeun JA,et al.Antimicrobial activity of 9-O-acyl and 9-O-benzyl-substituted berberrubines[J].Planta Medica,2000,66:361-363.
[156]Kim SH,Lee S J,Lee JH,et al.Antimicrobial activity of 9-O-acyl-and 9-O-alkylberberrubine derivatives[J].Planta Medica,2002,68:277-281.
[157]Zheng HY.Experimental and theoretical studies of p rotoberberine alkaloids on the mechanism of multiple activities(原小檗碱类生物碱作用差异的机制研究)[C].Tianjing:Tianjing Medical College,2004.
[158]Iwasa K,Moriyasu M,Yamori T,et al.In vitro cytotoxicity of the protoberberine-type alkaloids[J].Journal of Natural Products,2001,64:896-898.
[159]Orfila L,Rodr(?)guez M,Colman T,et al.Structural modification of berberine alkaloids in relation to cytotoxic activity in vitro[J].Journal of Natural Products,2000,71:449-456.
[160]Kobayashi Y,Yamashita Y,Fujii N,et al.Inhibitors of DNA topoisomerase I and II isolated from the cop tisrhizomes[J].Planta Medica,1995,61:414-418.
[161]Krishnan P,Bastow KF.The 92 position in berberine analogs is an important determinant of DNA topoisomerase II inhibition[J].Anticancer Drug Design,2000,15:255-264.
[162]Qin Y,Pang JY,Chen WH.Inhibition of DNA topoisomerase I by natural and synthetic monoand dimeric protoberberine alkaloids[J].Chemistry & Biodiversity,2007,4:481-487.
[163]Zhang WJ,Ou TM,Lu YJ.9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA[J].Bioorganic and Medicinal Chemistry Letters,2007,15:5493-5501.
[164]张灿,黄文龙.原小檗碱季铵类化合物的合成及抗心律失常活性研究[J].中国药科大学学报,2003,34(1):9-14.
[165]郑志仁,彭佶松,刘涤,等.黄芪毛状根的大量培养[J].植物生理学通讯,1997,33(2):133-134.
[166]芮和恺,忻晓君,顾慧芬,等.黄连的组织培养I.愈伤组织诱导及小檗碱含量测定[J].中药材,1990,13(3):3-5.
[167]李启任,杨峻芸,曹安飞,等.粉叶小檗愈伤组织的培养及小檗碱的含量[J].云南植物研究,1995,17(3):325-330.
[168]林启寿.中草药成分化学[M].科学出版社,1977.
[169]刘改芝,徐海伟,孙凯.穿心莲内酯衍生物的合成研究进展[J].有机化学,2008,28(2):201-209.
[170]金穿嘉,单文碘.黄连中小檗碱的薄层扫描定量测定法[J].药学通报,1982,17(3):17-18
[171]Wagner,H.;Wolff,P.M.Proceedings in Life Sciences,New York,1977,p.157.
[172]陈元柱,吴锵金,徐本杰,等.新马兜铃内酯的晶体结构[J].有机化学,1992,12,54-57.
[173]赵爱华,魏均娴.倍半萜类化合物生理活性研究进展[J].天然产物研究与开发,1995,7(4),65-70.
[174]邓文龙,聂仁吉,刘家玉,等.穿心莲制剂炎宁-3药理作用初步研究[J].中草药通讯,1978,(8),26-29.
[175]上海市穿心莲科研协作组.水溶性穿心莲内酯的研究[J].中草药通讯,1976,(3):10-18.
[176]苏州中药厂,南京药学院.穿心莲内酯的提取和与亚硫酸钠加成的工艺研究[J].中草药通讯,1976,(11):6-10.
[177]四川中药研究所药化室穿心莲研究组.脱水穿心莲内酯琥珀酸半酯单钾盐及其注射液的研究[J].中草药通讯,1978,8(1):1-6.
[178]王秀萍,费翰雨.穿心莲内酯糖苷衍生物的合成[J].中国药师,2005,8(6),446-448.
[179]Dai,G.F.;Xu,H.W.;Wang,J.F.;Liu,F.W.;Liu,H.M.Bioorganic and Medicinal Chemistry Letters.2006,16,2710.
[180]王新杨,徐浩,吴晓明,等.异穿心莲内酯衍生物的合成及其抗肿瘤活性[J].中国药科大学学报,2005,36,504-510.
[181]徐浩,黄文龙,张惠斌,等.穿心莲内酯硝甲基衍生物的合成[J].中国药物化学杂志,2005,15(4),212-217.
[182]韩光,杜钢军,许启泰,等.穿心莲内酯三马来酸单酯的合成及其解热抗炎作用研究[J].中国药学杂志,2005,40:628-631.
[183]唐才芳,奚国良,顾坤健,等.石吊兰素类似物的合成及其抗结核活性[J].药学学报,1981,16(10):787-782.
[184]Abbanat,Darren A.;Singh,Maya P.;Greenstein,Michael.Hongoquercins,new antibacterial agents from the fungus LL-23G227:fermentation and biological activity[J].Journal of Antibiotics,1998,51(8):708-714.
[185]Tsujimori,Hisayuki;Bando,Masahiko;Mori,Kenji.Synthetic microbial chemistry.XXXII.Synthesis and absolute configuration of hongoquercin A,an antibacterial sesquiterpene-substituted orsellinic acid isolated as a fungal metabolite[J].European Journal of Organic Chemistry,2000,(2):297-302.
[186]De Pascual Teresa,J.;Caballero,E.;Caballero,C.;et al.Trixagol,natural cyclogeranylgeraniol from Bellardia trixago(L.) All[J].Tetrahedron Letters,1978,(37):3491-3494.
[187]Bakkestuen,Anne Kristin;Gundersen,Lise-Lotte.Synthesis of(+)-trixagol and its enantiomer,the terpenoid side chain of(-)-agelasine E[J].Tetrahedron,2003,59(1):115-121.
[188]Lal,Bansi;Kansal,V.K.;Singh,Rekha;et al.An antiinflammatory active furochromone,norcimifugin from Cimicifuga foetida:isolation,characterization,total synthesis and;antiinflammatory activity of its analogs[J].Indian Journal of Chemistry,Section B:Organic Chemistry Including Medicinal Chemistry,1998,37B(9):881-893.
[189]Dekker,Theodor G.;Fourie,Theunis G.;Matthee,Elmare;et al.Studies of South African medicinal plants.Part 7.Rhinocerotinoic acid:a labdane diterpene with anti-inflammatory properties from Elytropappus rhinocerotis[J].South African Journal of Chemistry,1988,41(1):33-35.
[190]Gray,Christopher A.;Davies-Coleman,Michael T.;Rivett,Douglas E.A.An improved synthesis of rhinocerotinoic acid[J].Tetrahedron,2003,59(2):165-173.
[191]Yu,Boyang;Hirai,Yasuaki;Shoji,Junzo;et al.Comparative studies on the constituents of ophiopogonis tuber and its congeners.VI.Studies on the constituents of the subterranean part of Liriope spicata var.prolifera and L.muscari[J].Chemical & Pharmaceutical Bulletin,1990,38(7):1931-1935.
[192]Liu,Meizheng;Yu,Biao;Hui,Yongzheng.First total synthesis of 25(R)-ruscogenin-l-yl -D-xylopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranoside,an Ophiopogonis saponin from the tuber of Liriope muscari(Decneo)[J].Tetrahedron Letters,1998,39(5/6):415-418.
[193]Anthoni,Uffe;Christophersen,Carsten;Nielsen,Per H.Synthesis of naturally occurring 5-hydroxy-7,2',4',5'-tetramethoxy flavone and related compounds[J].Acta Chemica Scandinavica,1995,49(5):357-360.
[194]单杨,李高阳,汪秋安,等.橙皮苷半合成5种生物活性黄酮类化合物[J].有机化学,2008,28(6):1024-1028.
[195]李化军,栾新慧,赵毅民.3-O-甲基槲皮素的合成[J].有机化学,2004,24(12):1619-1621
[196]Formica JV,Regelson W.Review of the biology of quercetinand related bioflavonoids[J].Food and Chemical Toxicology,1995,33(12):1061-1080.
[197]Simoes CM,Schenkel EP,Bauer L,et al.A natural bioflavonoid product containingluteolin(II)[J].Journal of Ethnopharmacol,1988,22(3):281-293.
[198]李敬芬,孙志忠,佟德成.6-甲基-3',4'-亚甲二氧基-8-黄酮醋酸的合成及抗炎活性研究[J].中国现代应用药学杂志,2004,21(5):373-375.
[199]Lewis P.,Kaltia S.,WahalaK.The phase transfercatalyzedsynthesisof isoflavone-O-glucosides[J].Journal of the Chemical Society,Perkin Transactions l:Organic and Bio-Organic Chemistry,1998(16):2481-2484.
[200]陈莉莉.黄酮体羟甲基化衍生物合成及其药理作用研究[M].陕西师范大学硕士学位论文,
[1]中华人民共和国卫生部药典委员会.中华人民共和国药典:一部[Z].北京:化学工业出版社,2005,183-184.
[2]曹元宇 辑注.本草经[M].上海:上海科技出版社,1987:110.
[3]李时珍.本草纲目.卷十五[M].北京:人民卫生出版社,1957:973.
[4]吕华冲,王素贤,朱廷儒.禹州漏芦的化学成分研究[J].中草药,1989,20(11):2-5.
[5]果德安,崔亚君,楼之岑,等.华东蓝刺头化学成分的研究(I)[J].中草药,1992,23(1):3-5
[6]Lin Y.L.,Huang R.L.,Kuo Y.H.,et al.Thiophenes from Echinops grijsii Hance[J].The Chinese Pharmaceutical Journal,1999,51(3):201-211.
[7]Koike K.,Jia Z.,Nikaido T.,et al.Echinothiophene,a novel benzothiophene glycoside from the roots of Echinops grijsii[J].Organic Letters,1999,1(2):197-198.
[8]Liu Y.,Ye M.,Guo H.Z.,et al.New thiophenes from Echinops grijsii[J].Journal of Asian Natural Products Research,2002,4(3):175-178.
[9]果德安,楼之岑,刘治安.华东蓝刺头根挥发油成分的研究[J].中国中药杂志,1994,19(2):100-101.
[10]果德安,楼之岑,高从元,等.华东蓝刺头化学成分研究(II)[J].中草药,1992,23(10):512-514.
[11]刘玥,叶冠,崔亚君,等.华东蓝刺头地上部分化学成分研究[J].中草药,2002,33(1):18-20
[12]Lin C.C.,Yen M.H.,Chiu H.F.,et al.The pharmacological and pathological studies on Taiwan folk medicine(IV):The effects of Echinops grijsii and E.latifolius[J].American Journal of Chinese Medicine,1990,18(3-4):113-120.
[13]Lin C.C.,Lin C.H.The pharmacological and pathological studies on Taiwan folk medicine (IX):The hepatoprotective effect of the methanolic extract from Echinops grijsii[J].American Journal of Chinese Medicine,1993,21(1):33-44.
[14]Lin C.C.,Lin C.H.,Chiu H.F.,et al.The pharmacological and pathological studies on Taiwan folk medicine(VII):The anti-inflammatory effect of Echinops grijsii[J].American Journal of Chinese Medicine,1992,20(2):127-134.
[15]Cho K.,Ryw M.,Chin K.,et al.Thiophene compounds as antivirus,anti-inflammatory and immunoregulatory agents[P].JP:9502,665,1995-01-06.
[1]于德泉,杨峻山.喹啉-4-酮的 ~(13)C-NMR 化学位移.分析化学手册(第二版),第七分册:681
[2]娄红祥,左春旭.菱叶红景天化学成分研究[J].沈阳药学院学报,1990,7(2):145-146.
[3]Coogan C K,Horn D H S,Lamberton J A.The analysis of the spectra of two thiophene derivatives[J].Australian Journal of Chemistry,1965,18:723-729.
[4]冯宝民,裴月湖.柚皮中的化学成分[J].沈阳药科大学学报,2000,17(5):332-333.
[5]Selva A,Arnone A,Mondelli R,et al.Cardopatine and isocardopatine,two novel cyclobutane substances from Cardopatine Corymbosum[J].Phytochemistry,1978,17:2097-2100.
[6]袁久志,孙启时.蒙古栎化学成分的研究.中国中药杂志,1998,23(9):548-549.
[7]Lin Y L,Huang R L,Kuo Y H,et al.Thiophenes from Echinops grijsii Hance[J].Chin Pharm J,1999,51(3):201-211.
[8]Youla S.Tsantrios,Patricia L.Folkins,James F.Britien,and David N.Harpp.Approaches towards the synthesis of a sulfur analog of ergosterol peroxide.Canadian Journal of Chemistry,1992,70:158-164.
[9]刘悦,宋少江,徐绥绪,等.连翘化学成分研究.沈阳药科大学学报,2003,20(2):101-103.
[10]相婷,吴立军,林瑞红等.西南忍冬化学成分的结构鉴定II.中国药物化学杂志,1999,9(1):48-49.
[1]Hudson J.B.,Towers G.H.N.Therapeutic potential of plant photosensitizers[J].Pharmacology and Therapeutics,1991,49:188-222.
[2]Molinari M.Cell cycle checkpoints and their inactivation in human cancer[J].Cell Proliferation,2000,33(5):261-274.
[3]King R.W.,Deshaies K.J.,Peters J.M.,et al.How proteolysis drives the cell cycle[J].Science,1996,274(5293):1652-1659.
[4]Shankey V.T.,Rabinovitch R.,Bagwell B.,et al.Guidelines for implementation of clinical DNA cytometry[J].Cytometry,1993,14(5):472-477.
[5]谭卫东,金红,罗弟祥,等.抗肿瘤药物筛选中 MTT 法和 SRB 法的比较[J].天然产物研究与开发,1999,11(3):17-22.
[6]Knox J.R,Dodge A.Singlet oxygen and plants[J].Phytochemistry,1985,24(5):889-896.
[7]Evans C.,Weir D.,Scaiano J.C.,et al.Photochemistry of the botanical phototoxin,α-terthienyl and some related compounds[J].Photochemistry and Photobiology,1986,44:441-451.
[8]Scaiano J.C.,Evans C.,Arnason J.T.Characterization of the α-terthienyl radical cation:evidence against electron transfer to oxygen in vitro[J].Journal of Photochemistry and Photobiology B:Biology,1989,3(3):411-418.
[9]Towers G.H.N.,Hudson J.B.Potentially useful antimicrobial and antiviral phototoxins from plants[J].Photochemistry and Photobiology,1987,46:61-66.
[10]Hudson J.B.,Graham E.A.,Lam J.,et al.Ultraviolet-dependent biological activities of selected polyines of the Asteraceae[J].Planta Medica,1991,57(1):69-73.