【作者】 傅芃；

【导师】 张卫东；

【作者基本信息】 第二军医大学 ， 药物化学， 2009， 博士

【摘要】 本文对两种苔藓:大金发藓、红萼苔,以及药用植物刺齿枝子花进行了系统的化学成分研究,利用化学方法和色谱、光谱方法,共分离鉴定了60个化合物,10个为新化合物。其中,我们从苔藓植物大金发藓中分离并鉴定了2个具有新颖结构骨架的二氢黄酮并苯乙烯类化合物FP-DJFX-1,2,并对其生源进行了研究与推测,发现它们可能是由茋类分别于Z-和E-桂皮酸相互偶联生成的。另外,我们对部分新化合物进行了体外的抗肿瘤、抗炎活性的研究。1.两种苔藓植物的化学成分研究苔藓植物门(Bryophyta)包括苔纲[Hepaticae (Liverworts)?,藓纲[Musci(Mosses)]和角苔纲[Anthocerotae (Hornworts)?。苔藓类植物在我国被广泛应用于治疗外伤,烧伤,烫伤,感染,肺结核,肺炎,神经衰弱,惊厥等症。苔藓植物含有丰富的次生代谢产物,具有广泛的生物学活性。本文对2种苔藓植物:大金发藓(Polytrichum commune L.ex Hedw.)和红萼苔[Conoscypphus trapezioides (Sande Lac.) Schiffn]的化学成分进行了系统研究,共分得化合物30个,运用光谱分析技术IR,UV,EIMS,HRESIMS,1H NMR,13C NMR,2D NMR等鉴定了其中的22个化合物,分别为:FP-DJFX-1: Communin A,FP-DJFX-2: Communin B,FP-DJFX-3: Ohioensin H,FP-DJFX-4:β-谷甾醇,FP-DJFX-5: 7α-羟基谷甾醇,FP-DJFX-6:麦角甾醇,FP-DJFX-7: 6-乙酰基二氢吲哚,FP-DJFX-8:对羟基苯甲酸,FP-DJFX-9: 4-羟基-2-甲氧基苯甲酸,FP-DJFX-10:5-羟基-7-甲氧基色酮,FP-DJFX-11:5,7-二羟基-6-甲氧基香豆素-7-O-?-D-葡萄糖苷,FP-DJFX-12:蔗糖,FP-DJFX-13:?-D-呋喃阿洛酮糖,FP-DJFX-14:β-D-呋喃阿洛酮糖,FP-DJFX-15:乙二醇的11倍聚合体,FP-HET-1: Trapezioidesin A,FP-HET-2: Trapezioidesin B,FP-HET-3: (E)-2-(3,7-二甲基-2,6-二辛烯基)-4-甲氧基苯酚, FP-HET-4: (E)-3-(3,7-二甲基-2,6-二辛烯基)-4-甲氧基苯酚,FP-HET-5:白桦酸,FP-HET-6:齐墩果酸,FP-HET-7:庚内酰胺6倍聚合体。其中,FP-DJFX-1~3和FP-HET-1,2鉴定为5个新的化合物,FP-DJFX-1,2为两个结构新颖的二氢黄酮类的化合物;FP-DJFX-5~15和FP-HET-1~7为16个从这两种苔藓中首次分得的化合物。化合物Communin A,B(FP-DJFX-1,2)结构新颖,我们对其进行了生源学上的研究和推测,结论:它们可能是由茋类分别于Z-和E-桂皮酸相互偶联生成的。药理活性方面,采用四氮唑盐(Methyl-Thiazol-Tetrozolium, MTT)还原法筛选了化合物FP-DJFX-1~3的对A549(人肺癌细胞),LOVO(人肠癌细胞),MDA-MB-435(人乳腺细胞),HepG2(人肝癌细胞)6T-CEM(人T细胞白血病细胞)5个人肿瘤细胞株的体外药理活性筛选,结果显示,除化合物FP-DJFX-1以外,化合物FP-DJFX-2,FP-DJFX-3对5种人肿瘤细胞株均显示一定的细胞毒活性。这提示我们,FP-DJFX-1,2对人肿瘤细胞的细胞毒活性,可能取决于FP-DJFX-2中Z-型的构型的双键。2.药用植物刺齿枝子花的化学成分研究唇形科青兰属植物刺齿枝子花(Dracocephalum Peregrinum Linn.),生于高山草原石缝中,植物高15-25cm,6-8月开花,分布于中国新疆西北部(托里)。青兰属是唇形科中重要的属,常用作传统中药。化学成分研究报道,青兰属植物中多含有黄酮类化合物,萜类化合物,肉桂酸衍生物及挥发油。关于刺齿枝子花(Dracocephalum Peregrinum)的化学成分及药理活性的报道很少,本文对其化学成分进行了系统的研究,运用光谱分析技术IR,UV,EIMS,HRESIMS,1H-NMR,13C-NMR,2DNMR等鉴定了其中的38个化合物,分别为:FP-CCZZH-1: Peregrinumin A,FP-CCZZH-2: Peregrinumin B,FP-CCZZH-3: Peregrinumin C,FP- CCZZH-4: Peregrinumcin A,FP-CCZZH-5: Peregrinumin D,FP- CCZZH-6:木犀草素,FP-CCZZH-7: 5, 7, 3’-三羟基-4’-甲氧基黄酮,FP-CCZZH-8:山奈酚,FP-CCZZH-9:刺槐素,FP-CCZZH-10: 5, 3’, 4’-三羟基-3, 7-二甲氧基黄酮,FP-CCZZH-11: 5-羟基-3’, 4’, 6, 7-四甲氧基黄酮,FP-CCZZH-12:山奈酚-7-O-β-D-葡萄糖苷,FP-CCZZH-13:刺槐素-7-O-β-D-葡萄糖苷,FP-CCZZH-14: 5, 6, 7, 4’-四羟基黄酮-7-O-β-D-葡萄糖苷,FP-CCZZH-15:异槲皮苷,FP-CCZZH-16:槲皮苷,FP- CCZZH-17: 3, 5, 7-三羟基-4’-甲氧基黄酮-3-O-α-L-鼠李糖苷,FP- CCZZH-18: 5, 7-二羟基-4’-甲氧基黄酮-7-O-α-L-鼠李糖基(1→6)-β-D-葡萄糖苷,FP-CCZZH-19:咖啡酸,FP-CCZZH-20:咖啡酸甲酯,FP-CCZZH-21:阿魏酸,FP-CCZZH-22:反式对羟基桂皮酸,FP- CCZZH-23:绿原酸,FP-CCZZH-24: 3-羟基苯甲酸,FP-CCZZH-25: 3, 4-二羟基苯甲酸,FP-CCZZH-26: 4-羟基-3-甲氧基苯甲醛,FP-CCZZH-27:对羟基苯甲酸葡萄糖苷,FP-CCZZH-28:苯-β-D-葡萄糖苷,FP- CCZZH-29: 2R-野樱苷,FP-CCZZH-30: 3-羰基熊果酸,FP-CCZZH-31:熊果酸,FP-CCZZH-32:齐墩果酸,FP-CCZZH-33:羽扇豆醇,FP- CCZZH-34:白桦酸,FP-CCZZH-35:白桦酯醇,FP-CCZZH-36:胡萝卜素,FP-CCZZH-37:胡萝卜苷,FP-CCZZH-38:豆甾醇。其中FP-CCZZH-1~5为5个新化合物,FP-CCZZH-12,13,19,20,22,25,29,30,31,32为10个首次从刺齿枝子花中分得的化合物。我们对新化合物FP-CCZZH-1~4进行了体外抗炎活性的初步检测,结果表明,NO抗炎模型检测中化合物FP-CCZZH-1~4在检测浓度为100 ?g/ml时均显示一定的体外抗炎活性;而NF-?B抗炎模型检测中仅有FP-CCZZH-2,3在浓度为100 ?g/ml时显示微弱的体外抗炎活性。更多还原

【Abstract】 Two bryophytes, Polytrichum commune and Conoscyphus trapezioides and the medicinal plant Dracocephalum peregrinum were phytochemically investigated in this paper. A total of 60 compounds were obtained and their structures were determined on the basis of extensive chemical and spectroscopic means. Two novel flavonones coupled with styryls, FP-DJFX-1~2, together with 8 new compounds were identified. FP-DJFX-1~2 could hypothetically be derived from the coupling of stilbenes with Z- and E-cinnamic acids, respectively.1. Studies on the Chemical Constituents of Polytrichum commune and Conoscypphus trapezioidesThe bryophyta, which comprise more than 24,000 species worldwide, are taxonomically placed between algae and pteridophytes. Collectively, they represent several quite separate evolutionary lines and are classified into three coordinate phyla: liverworts, mosses and hornworts. Bryophytes have been widely used as medicinal plants for the treatment of external injury, adustum, empyrosis, infection, pulmonary tuberculosis, neurastheria convulsion. And they are composed of various types of secondary metabolite which show significant biological activities.In this paper, Polytrichum commune L.ex Hedw. and Conoscypphus trapezioides (Sande Lac.) Schiffn. were phytochemically investigated. A total of 30 compounds were obtained and 22 of them were determined on the basis of spectral analysis: FP-DJFX-1: Communin A, FP-DJFX-2: Communin B, FP-DJFX-3: Ohioensin H, FP-DJFX-4: ?-sitosterol, FP-DJFX-5: 7αhydroxylsitosterol,FP-DJFX-6: ergosterol, FP-DJFX-7: methylindoline -6-carboxylate, FP-DJFX-8: 4-hydroxybenzoic acid, FP-DJFX-9: 4- hydroxy-2-methoxybenzoic acid, FP-DJFX-10:5-hydroxy-7-methoxy-4H- chromen-4-one, FP-DJFX-11 : 5-hydroxy-6-methoxy-7-O-β-D-glucosyl coumarin, FP-DJFX-12:sucrose, FP-DJFX-13:?-D-furanallulose,FP- DJFX-14 :β-D-uranallulose, FP-DJFX-15 : 3,6,9,12,15,18,21,24,27,30- decaoxadotriacontane-1,32-diol. FP-HET-1: Trapezioidesin A, FP-HET-2: Trapezioidesin B, FP-HET-3: (E)-2-(3,7-dimethylocta-2,6-dienyl)-4- methoxyphenol, FP-HET-4: (E)-3-(3,7-dimethylocta-2,6-dienyl)-4- methoxyphenol, FP-HET-5: betulinic acid, FP-HET-6: oleanolic acid, FP-HET-7: 1,8,15,22,29,36-hexaazacyclodotetracontane-2,9,16,23,30,37- hexaone.Among them, FP-DJFX-1~3 and FP-HET-1, 2 are five new compounds, FP-HET-7 is a new natural products and FP-DJFX-5~15 and FP-HET-1~7 were isolated from these plants for the first time. FP-DJFX-1~3 might be derived from cinnamic acid and 3,5-dioxohexanoice acid via different pathways. FP-DJFX-1 and FP-DJFX-2 apparently arised from the coupling of stilbenes with Z- or E-cinnamic acids, respectively. FP-DJFX-2 and FP-DJFX-3 exhibited cytotoxicity against A-549 lung carcinoma, LOVO bowel carcinoma, MDA-MB-435 breast adenocarcinoma, HepG2 hepatoma carcinoma and 6T-CEM T cell leukemia cell lines. However, FP-DJFX-1, the isomer to FP-DJFX-2, showed no cytotoxicity in the cytotoxic assay. This implied that the Z-geometry double bond in FP-DJFX-2 played an important role in the cytotoxicity against these human tumor cell lines.2. Studies on the Chemical Constituents of Dracocephalum peregrinum Dracocephalum peregrinum, Labiatae, likes growing in the crack of stones on alpine steppe. which usually grows 15~25 cm high and flowers from June to August, distributes in northwest of the Xin Jiang Province in China.Genus Dracocephalum was an important member of the Labiatae family. Several species of Dracocephalum were used in Traditional Chinese Medicine. Chemical investigation on these species resulted in the isolation of flavanoids, terpenoids, cinnamic acid derivatives and volatile oils, but very few chemical and pharmacological study was reported on Dacocephalum peregrinum until now.In our further phytochemical investigation on Dracocephalum peregrinum, 40 compounds were isolated and 38 of them were identified by spectral analysis: FP-CCZZH-1: Peregrinumin A, FP-CCZZH-2: Peregrinumin B, FP-CCZZH-3: Peregrinumin C, FP-CCZZH-4: Peregrinumcin A, FP-CCZZH-5: Peregrinumin D, FP-CCZZH-6: luteolin, FP-CCZZH-7: 5,7,3’-trihydroxyl-4’-methoxylflavone, FP-CCZZH-8: kaempferol, FP-CCZ ZH-9: acacetin, FP-CCZZH-10: 5,3’,4’-trihydroxyl-3, 7-dimethoxylflavone, FP-CCZZH-11: 5-hydroxyl-3’,4’,6,7-tetramethoxyl flavone, FP-CCZZH -12: kaempferol-7-O-β-D-glucoside, FP-CCZZH-13: acacetin-7-O-β-D-glucoside, FP-CCZZH-14: 5,6,7,4’-tetrahydroxylflavone -7-O-β-D-glucoside, FP-CCZZH-15: isoquercitrin, FP-CCZZH-16: quercitrin, FP-CCZZH-17: 3,5,7-trihydroxyl-4’-methoxylflavone-3-O-?-L- rhamnoside, FP-CCZZH-18: 5,7-dihydroxyl-4’-methoxyl flavone-7-O-?-L- rhamnosyl(1?6)-?-D-glucoside, FP-CCZZH-19: caffeic acid, FP-CCZZH- 20: methyl caffeate, FP-CCZZH-21: ferulic acid, FP-CCZZH-22: trans-P- hydroxycinnamic acid, FP-CCZZH-23: caffeotannic acid, FP-CCZZH-24: 3-hydroxybenzoic Acid , FP-CCZZH-25: 3,4-dihydroxybenzoic Acid, FP- CCZZH-26: 4-hydroxy-3-methoxy benzaldehyde, FP-CCZZH-27: P- hydroxybenzcic acid glucoside, FP-CCZZH-28: benzene-β-D-glucoside, FP- CCZZH-29: 2R-prunasin, FP-CCZZH-30: 3-carbonylursolic acid, FP- CCZZH-31: ursolic acid, FP-CCZZH-32: oleanolic acid, FP-CCZZH-33: lupeol, FP-CCZZH-34: betulinic acid, FP-CCZZH-35: betulin, FP- CCZZH-36: carotene, FP-CCZZH-37: daucosterol, FP-CCZZH-38: stigmasterol.Among them, FP-CCZZH-1~5 are five new compounds and FP-CCZZH-12, 13, 19, 20, 22, 25, 29, 30, 31, 32 were isolated from this plants for the first time.FP-CCZZH-1~4 were tested for effects on NO and NF-?B activity. Among the compounds tested, FP-CCZZH-1~4 showed good inhibitory activities on NO production induced by LPS at dose of 100 ?g/ml. But only FP-CCZZH-2 and 3 showed weak effects on NF-?B activity at dose of 100 ?g/ml.更多还原