中麻黄的化学成分研究

研究中麻黄(Ephedra intermedia Schrenk et C.A.Mey.)干燥草质茎的化学成分及其抗哮喘活性。应用硅胶柱色谱、Sephadex LH-20柱色谱、Toyopreal HW-40C柱色谱以及半制备型高效液相色谱等多种手段对中麻黄草质茎的50%丙酮提取物进行化学成分研究,从中分离鉴定了22个化合物,根据其理化性质和波谱学数据鉴定其结构,分别为4-甲氧基肉桂酸(1)、肉桂酸(2)、ω-hydroxypropioguaiacone(3)、threo-8S-7-methoxysyringylglycerol(4)、3-(2,4′-dihydroxy-3′,5′-dimethoxyphenyl)propanoic acid(5)、8-hydroxy-9-methyl-7-(4-hydroxy-3,5-dimethoxyphenyl)-7-propanone(6)、3-羟基-1-(4-羟基-3,5-二甲氧基苯基)-1-丙酮(7)、2-羟基-1-(4-羟基-3-甲氧基)苯基-1-丙酮(8)、异咖啡酸甲酯(9)、trans-syringin(10)、cis-syringi...     

桂枝化学成分研究北大核心CSCD

桂枝是临床常用中药,本课题组前期发现桂枝乙醇提取物具有抑制程序性细胞坏死的生理活性。为进一步阐明桂枝的化学成分和更好地开发利用桂枝药用资源,该文采用大孔吸附树脂、硅胶柱色谱、Sephadex LH-20柱层析、制备型高效液相色谱等多种方法对桂枝75%乙醇提取物进行了研究。此次报道从中得到的13个单体化合物,它们的结构经波谱数据分析及文献对照鉴定为脱落酸(1)、蚱蜢酮(2)、2,3-二羟基-1-(4-羟基-3,5-二甲氧基苯基)-1-丙酮(3)、赤型-1,2,3-三羟基苯丙烷(4)、1-苯基-1,3-丙二醇(5)、香豆素(6)、肉桂酸(7)、对羟基肉桂酸(8)、邻羟基肉桂酸(9)、邻甲氧基肉桂酸(10)、肉桂醛(11)、阿魏酸(12)、咖啡酸乙酯(13)。其中1-5、12和13为首次从桂枝中分离得到。     

美飞蛾藤（Porana spectabilis Kurz）植物中的化学成分

首次从旋花科飞蛾藤属植物美飞蛾藤（Porana spectabilis Kurz)醇提物中分离鉴定了8个已知化合物,通过波谱方法确定了它们的结构分别为东莨菪素（7－hydroxy-6-methoxycoumarin or soopoletin)(1),东莨菪甙（scoplin)(2);咖啡酸乙酯（ethyl caffeate)(3)和3,5－二羟基肉桂酸（3－（3,5－dihydroxyphenyl)-2E-propenoic acid)(4);α－（D）－甲基呋喃果糖甙（Methylα-Dfrucofuranoside)(5)β－（D）－甲基吡喃果糖甙（Methyl β－D-frucopyranoside)(6);2,5-二羟基基苯甲酸（2,5－dihydroxybenzoic acid)(7);丁香脂素－4－O－β－D－吡喃葡萄糖甙（＋）syringaresinol-4-O-β-(D)-glucopyranoside)(8)。     

藏药翁布的酚性成分研究

从藏药翁布(Myricaria germanica)的60％丙酮提取物中进行了进一步研究,从中共分离得到了11个化合物.利用光谱和波谱分析法,分别鉴定为阿魏酸(1),松柏醇(2),阿魏酸葡糖苷(3),异落叶松脂醇(4),咖啡酸(5),对羟基桂皮酸(6),没食子酸(7),3,5-二羟基-4-甲氧基苯甲酸(8),杜鹃醇(9),3-甲氧基-4-羟基-苯甲酸(10)和3,4,5-三羟基肉桂酸(11).化合物1～11均为首次从该植物中分得,其中1～6和8～11为首次从水柏枝属植物中分离得到.     

血人参石油醚部位化学成分研究

为深入探究血人参中的活性物质成分，该文采用硅胶柱色谱、Sephadex LH-20柱色谱、半制备高效液相色谱以及重结晶等方法对血人参石油醚部位进行了系统分离纯化，并利用现代波谱技术对分离得到的单体化合物进行结构鉴定。结果表明：从血人参石油醚部位共分离得到22个单体化合物，分别鉴定为β-谷甾酮(1)、豆甾烷3,6-二酮(2)、6β-羟基-豆甾-4-烯-3-酮(3)、(22E)-5α,8α-epidioxyergosta-6, 22-dien-3β-ol(4)、美迪紫檀素(5)、sativan(6)、2′,4′-二羟基查尔酮(7)、6,7-dimethoxy-4-hydroxy-1-naphthoic acid(8)、对羟基苯甲酸乙酯(9)、2,4-二羟基苯甲酸乙酯(10)、(9E,11E)-13-oxo-9,11-ocatadecadienoic acid(11)、(9E,11E)-13-oxo-9,11-octadecadienoic acid methyl ester(12)、9-oxo-10E,12E-octadecadienoic acid methyl ester(13)、9-...     

紫茎泽兰中的酚类化学成分

从紫茎泽兰(Eupatorium adenophorum Spreng.)乙醇提取物中分离得到11个酚类化合物。通过波谱分析,分别鉴定为咖啡酸(1)、阿魏酸(2)、芥子醛(3)、苯乙基阿魏酯(4)、3,4-二羟基苯甲酸(5)、4-羟基-3-甲氧基苯甲酸(6)、3,4-二甲氧基苯甲酸(7)、没食子酸(8)、3-(3,4-二羟基苯基)-1-丙醇(9)、2-香豆酸-β-D-吡喃葡萄糖苷(10)和4-O-β-D-葡萄糖苷-3,5-二甲氧基苯基-乙基酮(11)。化合物3~9和11为首次从紫茎泽兰中分离得到。     

华石斛化学成分研究

为了解华石斛(Dendrobium sinense)的化学成分,采用多种柱色谱技术从其全草乙醇提取液中分离纯化了10个化合物,经波谱分析分别鉴定为:鼓槌石斛素(1)、2′,4′-二羟基查尔酮(2)、2,5,7-三羟基-4-甲氧基-9,10-二氢菲(3)、4,7-二羟基-2,3-二甲氧基-9,10-二氢菲(4)、2,5-二羟基-3,4-二甲氧基-9,10-二氢菲(5)、2,7-二羟基-3,4,6-三甲氧基-9,10-二氢菲(6)、(E)松柏醛(7)、反式对羟基肉桂酸酯(8)、对羟基苯丙酸甲酯(9)和十二元内环酯(10)。所有化合物均为首次从华石斛中分离得到,其中化合物2、6、7和10对乙酰胆碱酯酶具有一定的抑制活性。     

薏苡糠壳的化学成分及其种子萌发活性研究

为了解薏苡(Coixlachryma-jobi)糠壳的化学成分,利用多种柱色谱技术对其乙醇提取物乙酸乙酯萃取部位进行分离,经波谱数据分析鉴定了15个化合物,分别为香豆酸(1)、香豆酸甲酯(2)、2-羟乙基-香豆酸酯(3)、咖啡酸甲酯(4)、阿魏酸甲酯(5)、(E)-3-(4-甲氧基苯基)丙烯酸(6)、2,3-二羟基-1-(4-羟基-3-甲氧基苯基)-1-丙酮(7)、2,3-二羟基-1-(4-羟基-3,5-二甲氧基苯基)-1-丙酮(8)、对羟基苯甲酸(9)、3-羟基-4-甲氧基苯甲酸(10)、1,3,5-三甲氧基苯(11)、methyl (3-hydroxy-2-oxo-2,3-dihydroindol-3-yl)-acetate (12)、尿囊素(13)、2-(2-羟乙基)-3-甲基反丁烯二酸(14)和油酸(15),其中化合物3、7、12、13和14为首次从薏苡中分离得到。活性测试结果表明,化合物1、2、9、10和11对种子萌发具有较强的抑制作用。     

霍山石斛化学成分研究

研究霍山石斛Dendrobium huoshanense Tang et Cheng茎的化学成分。应用硅胶、Sephadex LH-20、MCI-gel、Rp-18结合Semi-prep HPLC技术进行分离纯化,从霍山石斛茎中分离得到29个化合物,分别鉴定为4,4′-二羟基-3,5-二甲氧基联苄(1)、batatasin Ⅲ(2)、5,4′-二羟基-3-甲氧基联苄(3)、二氢松柏醇二氢对羟基桂皮酸酯(4)、对羟基苯丙酸甲酯(5)、二氢松柏醇(6)、二氢阿魏酸(7)、松柏醛-4-O-β-D-吡喃葡萄糖苷(8)、4-烯丙基-2,6-二甲氧-苯基葡萄糖苷(9)、erythrosyringoylglycerol-4-O-β-D-glucopyranoside(10)、3,4,5-trihydroxyallylbenzene-3-O-β-D-glucopyranosyl-4-O-β-D-glucopyranoside(11)、(7S,8R)syringylglycerol-8-O-4′-sinapyl ether 4-O-β-D-glucopyranoside(12)、3,4-二羟基-5-甲氧基苯甲醛(13)、对羟基苯甲酸(14)、5-hydroxylated isobenzofuran-1(3H)-one(15)、3,5-二甲氧基-4-羟基-苯甲醛(16)、4-羟基-3-甲氧基苯甲醛(17)、3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside(18)、天麻苷(19)、丁香脂素(20)、丁香脂素-4-O-β-D-葡萄糖苷(21)、丁香脂素-4,4′-O-β-D-二葡萄糖苷(22)、柚皮素(23)、2,6-二甲氧基对苯醌(24)、5-羟甲基糠醛(25)、tetrahydro-5-oxo-2-furancarboxylic acid methyl ester(26)、焦谷氨酸甲酯(27)、川芎哚(28)和尿嘧啶核苷(29)。其中化合物5～19、21～29位为首次从该植物中分离得到,化合物8、10、11、15、16、18、26、28为首次从石斛属中分离得到。     

岩木瓜茎干化学成分及PTP1B抑制活性研究

综合运用天然产物化学分离、纯化技术从岩木瓜茎干中分离得到18个化合物,结合各化合物理化性质和光谱数据鉴定其结构,依次为对羟基苯乙酮(1)、对羟基苯甲酸(2)、对羟基苯甲酸乙酯(3)、3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one(4)、咖啡酸(5)、咖啡酸乙酯(6)、对羟基苯甲醛(7)、咖啡酸甲酯(8)、对羟基桂皮酸(9)、水杨酸(10)、原儿茶酸(11)、3,5-二羟基-4-甲氧基苯甲酸(12)、对醛基苯基-1-O-葡萄糖苷(13)、色氨酸(14)、豆甾-3,6-二酮(15)、β-谷甾酮(16)、5α-9(11)-豆甾烯-3β-醇(17)和胡萝卜苷(18)。这些化合物均为首次从该植物分离得到,其中化合物4,6,16和17为首次从该属植物中分离得到。对从岩木瓜中分离得到的46个化合物进行PTP1B抑制活性筛选,11个化合物具有PTP1B抑制活性,IC50值在1.0~37.0μM之间。     

Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways

Caffeic acid phenethyl ester has been shown to have anti-inflammatory and anti-cancer effects. We examined the effects of caffeic acid phenethyl ester on lipopolysaccharide-induced production of nitric oxide and prostaglandin E(2), and expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages. We also investigated the effects of caffeic acid phenethyl ester on lipopolysaccharide-induced septic shock in mice. Our results indicate that caffeic acid phenethyl ester inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production in a concentration-dependent manner and inhibits inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 cells, without significant cytotoxicity. To further examine the mechanism responsible for the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by caffeic acid phenethyl ester, we examined the effect of caffeic acid phenethyl ester on lipopolysaccharide-induced nuclear factor-kappaB activation and the phosphorylation of mitogen-activated protein kinases. Caffeic acid phenethyl ester treatment significantly reduced nuclear factor-kappaB translocation and DNA-binding in lipopolysaccharide-stimulated RAW 264.7 cells. This effect was mediated through the inhibition of the degradation of inhibitor kappaB and by inhibition of both p38 mitogen-activated protein kinase and extracellular signal-regulated kinase phosphorylation, at least in part by inhibiting the generation of reactive oxygen species. Furthermore, caffeic acid phenethyl ester rescued C57BL/6 mice from lethal lipopolysaccharide-induced septic shock, while decreasing serum levels of tumor necrosis factor-alpha and interleukin-1beta. Collectively, these results suggest that caffeic acid phenethyl ester suppresses the induction of cytokines by lipopolysaccharide, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression, by blocking nuclear factor-kappaB and p38/ERK activation. These findings provide mechanistic insights into the anti-inflammatory and chemopreventive actions of caffeic acid phenethyl ester in macrophages.     

Synthesis of a series of caffeic acid phenethyl amide (CAPA) fluorinated derivatives: Comparison of cytoprotective effects to caffeic acid phenethyl ester (CAPE)

A series of catechol ring-fluorinated derivatives of caffeic acid phenethyl amide (CAPA) were synthesized and screened for cytoprotective activity against H₂O₂ induced oxidative stress in human umbilical vein endothelial cells (HUVEC). CAPA and three fluorinated analogs were found to be significantly cytoprotective when compared to control, with no significant difference in cytoprotection between caffeic acid phenethyl ester (CAPE) and CAPA.     

Mechanism of toxicity of esters of caffeic and dihydrocaffeic acids

Ten esters each of caffeic acid and dihydrocaffeic acid have recently been synthesized. Cytotoxicity evaluations of these esters versus L1210 leukemia and MCF-7 breast cancer cells in culture have led to the delineation of substantially different QSAR for each series. The L1210 QSAR for dihydrocaffeic acid esters resembles the QSAR obtained for simple phenols and estrogenic phenols. However, the QSAR pertaining to the caffeic acid esters differs considerably from its sister QSAR. This difference may be attributed to the presence of the olefinic linkage in the side chain. The octyl ester of caffeic acid is nearly ten times as toxic to the leukemia cells than the widely studied phenethyl ester, CAPE.     

Drastic effect of several caffeic acid derivatives on the induction of heme oxygenase-1 expression revealed by quantitative real-time RT-PCR

Among antioxidative polyphenols, caffeic acid esters such as caffeic acid phenethyl ester (CAPE) and chlorogenic acid are contained in propolis, vegetables and coffee. In this study, we compared the efficacy of some polyphenols on the activation level of a cytoprotective heme oxygenase-1 (HO-1) gene in RAW264.7 mouse macrophage cells using quantitative real-time RT-PCR. The quantitative study revealed a variety of activation level of HO-1 gene by the chemicals. CAPE and caffeic acid ethyl ester (CAEE) at the final concentration of 2 muM drastically activated the HO-1 gene to 39.2-fold and 20.1-fold, respectively. Curcumin, structurally related with caffeic acid and an element of turmeric, induced the HO-1 gene to 5.8-fold. In contrast, no activation was observed by other caffeic acid esters such as chlorogenic acid and rosmarinic acid. Higher concentrations were necessary for the activation by an antioxidant cysteamine and the electrophile diethyl maleate. Although the inducible activities of CAPE and chlorogenic acid were distinctly different, they showed similar reductive capacities when determined by cyclic voltammetry. These results show that the drastic activation of HO-1 gene by CAPE and CAEE is dependent upon their chemical structures, rather than the reductive activity of polyphenols, possibly reflecting the physiological effects of the nutritional elements.     

Design and synthesis of novel nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors from caffeic acid phenethyl ester

A series of nitrogen-containing polyhydroxylated aromatics from caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase inhibitors. Most of these compounds exhibited potent inhibitory activities at micromolar concentrations against HIV-1 integrase in the 3′-end processing and the strand transfer. Their key structure–activity relationship was also discussed.     

Effect of ionic liquids on enzymatic synthesis of caffeic acid phenethyl ester

Although caffeic acid phenethyl ester (CAPE), an active flavonoid, plays an important role in the antioxidant activity of honeybee propolis, the isolation of CAPE from honeybee propolis is time-consuming due to wide variety of impurities present. Therefore, biochemical method to synthesize CAPE was investigated in this study. Since ionic liquids (ILs) possess some unique characteristics as appreciated alternatives to conventional solvents for certain biotransformation, the effect of ILs as reaction media for enzymatic synthesis of CAPE was assessed. Several factors including substrate molar ratio, and reaction temperature affecting the conversion yield of lipase-catalyzed CAPE synthesis were also investigated. Reaction yields were significantly higher in hydrophobic ILs than in hydrophilic ILs (almost zero). Among nine hydrophobic ILs tested, the highest conversion of synthetic reaction was obtained in 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([Emim][Tf(2)N]). A reaction temperature of 70 °C was found to give high conversion. In addition, optimal substrate molar ratio between phenethyl alcohol and caffeic acid (CA) was decreased significantly from 92:1 to 30:1 when ILs were used instead of isooctane.     

Effect of propolis on human cartilage and chondrocytes

Propolis, a natural product derived from plant resins collected by the honeybees, has been used for thousands of years in folk medicine for several purposes. The extract that contains amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, terpenes and caffeic acid, possesses several biological activities such as anti-inflammatory, immunostimulatory, anti-viral and anti-bacterial. In this study, we assay the effects of propolis extract on the production of key molecules released during chronic inflammatory events as nitric oxide (NO) and glycosaminoglycans (GAGs) in cultures of human cartilaginous tissues and chondrocytes, stimulated with interleukin-1beta (IL-1beta). We observed that this natural compound and its active principle, caffeic acid phenethyl ester (CAPE), were able to contrast the harmful effects of IL-1beta.Our data clearly demonstrated the protective action of propolis in cartilage alteration, that appears greater than that elicited by indomethacin, commonly employed in joint diseases.     

Nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors: synthesis, structure-activity relationship analysis, and biological activity

Four series of forty-five nitrogen-containing polyhydroxylated aromatics based on caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase (IN) inhibitors. Most of these compounds inhibited IN catalytic activities in low micromolar range. Among these new analogues, compounds 9e and 9f were the most potent IN inhibitors with IC(50) value of 0.7 μM against strand transfer reaction. Their key structure-activity relationships were also discussed.     

The effect of propolis and its components on eicosanoid production during the inflammatory response

To investigate the possible mechanism of the therapeutic action of propolis, we studied: (a) the effect of propolis, its components, caffeic acid phenethyl ester (CAPE), caffeic acid (CA), quercetin and naringenin, as well as the synthetic compounds indomethacin (IM) and nordihydroguaiaretic acid (NDGA), and a novel lipoxygenase inhibitor N,N′-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)isourea (DCHCU) on eicosanoid production by mouse peritoneal macrophages in vitro; (b) the effect of IM, NDGA, CA, CAPE, DCHCU and propolis on eicosanoid production during acute inflammation in vivo; and (c) the ex vivo and in vivo effect of dietary propolis on arachidonic acid metabolism. The ethanol extract of propolis suppressed prostaglandin and leukotriene generation by murine peritoneal macrophages in vitro and during zymosan-induced acute peritoneal inflammation in vivo. Dietary propolis significantly suppressed the lipoxygenase pathway of arachidonic acid metabolism during inflammation in vivo. CAPE was the most potent modulator of the arachidonic acid cascade among the propolis components examined.     

Optimization of lipase-catalyzed synthesis of caffeic acid phenethyl ester in ionic liquids by response surface methodology

Lipase-catalyzed caffeic acid phenethyl ester (CAPE) synthesis in ionic liquid, 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([Emim][Tf₂N]), was investigated in this study. The effects of several reaction conditions, including reaction time, reaction temperature, substrate molar ratio of phenethyl alcohol to caffeic acid (CA), and weight ratio of enzyme to CA, on CAPE yield were examined. In a single parameter study, the highest CAPE yield in [Emim][Tf₂N] was obtained at 70 °C with a substrate molar ratio of 30:1 and weight ratio of enzyme to CA of 15:1. Based on these results, response surface methodology (RSM) with a 3-level-4-factor central composite rotatable design (CCRD) was adopted to evaluate enzymatic synthesis of CAPE in [Emim][Tf₂N]. The four major factors were reaction time (36–60 h), reaction temperature (65–75 °C), substrate molar ratio of phenethyl alcohol to CA (20:1–40:1), and weight ratio of enzyme to CA (10:1–20:1). A quadratic equation model was used to analyze the experimental data at a 95 % confidence level (p < 0.05). A maximum conversion yield of 99.8 % was obtained under the optimized reaction conditions [60 h, 73.7 °C, substrate molar ratio of phenethyl alcohol to CA (27.1:1), and weight ratio of enzyme to CA (17.8:1)] established by our statistical method, whereas the experimental conversion yield was 96.6 ± 2 %.