相转移催化合成11-脱氧甘草次酸-3-位酯类衍生物

以甘草次酸为原料 ,经还原制得 1 1 -脱氧甘草次酸 ,然后在聚苯乙烯固载化聚乙二醇 40 0( PS- PEG- 40 0 )的催化下。合成了七种具有潜在药理活性和应用前景的 1 1 -脱氧甘草次酸 - 3-位酯类衍生物。合成方法简单 ,产率较高 ,后处理方便     

甘草次酸的结构修饰及生物活性研究进展

甘草次酸是甘草中重要的黄酮之一,其具有明显的抗炎、抗溃疡、抗肿瘤、抗病毒、抗氧化、美白等活性,在食品、药品等行业得到广泛应用,并越来越受到科研人员的关注。目前,甘草次酸结构修饰主要集中在C-3、C-30、C-11位。就甘草次酸结构修饰及甘草次酸衍生物的生物活性进行了探讨,为甘草次酸衍生物的合成及甘草次酸的开发提供参考依据。     

甘草次酸衍生物的制备工艺研究进展

甘草次酸具有3-位羟基、11-位羰基和30-位羧基官能团,按照排列组合C31+C32+C33=7,可有7类衍生物。即3-位羟基结构修饰衍生物、11-位羰基结构修饰衍生物、30-位羧基结构修饰衍生物、3-羟基和11-位羰基结构同步修饰衍生物、3-位羟基和30-位羧基结构同步修饰衍生物、11-位羰基和30-位羧基结构同步修饰衍生物和3-位羟基、11-位羰基和30-位羧基结构同步修饰衍生物。对7类衍生物的制备工艺进行了详细的综述,以期对甘草次酸衍生物的制备提供综合参考。     

基于网络药理探讨甘草及甘草次酸药效/副作用的分子作用机制研究

目的:探讨基于网络药理探讨甘草及甘草次酸药效/副作用的分子作用机制,为临床合理用药提供依据.方法:基于网络药理,从药理学分析平台(TCMSP)中寻找甘草及其中甘草次酸相关化学成分.根据二者的性质、药效,选择口服生物利用度(OB)≥50.0％(甘草)/OB≥17.0％(甘草次酸),类药效(DL)≥0.18作为筛选条件,寻找与候选化合物相关的潜在靶点,构建其成分-靶点,靶点-疾病及副作用的网络图.结果:选择OB≥50.0％(甘草),OB≥17.0％(甘草次酸),DL≥0.18作为筛选条件,结果表明:共43个候选化合物均具有良好的OB、DL特性;43个候选化合物与潜在的靶标之间构建相互作用网络图,图中共计结点136个,潜在靶标93个,网络线合计744条,甘草次酸具有6个潜在靶标,说明甘草及甘草次酸的成分与靶点蛋白的分子良好的结合能力.靶点-疾病相互作用网络图中,甘草及甘草次酸合计结点102个,其中44中相关疾病,58个靶标,合计边57个,一个靶蛋白能与多个疾病相互作用.罗列甘草次酸常见的不良反应绘制网络图,不良反应共有13种.结论:基于网络药理,验证了甘草及甘草次酸的基本药理作用及相关机制,以及甘草次酸的副作用,能为临床合理用药提供参考和依据.     

氮端Fmoc保护11-脱氧甘草次酸二肽类衍生物的合成

为获得高药效甘草次酸衍生物,以甘草次酸为原料,经过克莱门森还原得到11-脱氧甘草次酸,所得产物经溴乙烷乙酯化制得11-脱氧甘草次酸-30-乙酯,之后在THF溶液(四氢呋喃)中与Fmoc-Met-OH(Fmoc保护的甲硫氨酸)在DCC/DMAP中耦合制得11-脱氧甘草次酸-30-乙酯-3-Fmoc保护甲硫氨酸,然后在V(CHCl2)∶V(二乙胺)=1∶1溶液中脱去Fmoc保护基得到11-脱氧甘草次酸-30-乙酯-3-甲硫氨酸,再在THF溶液中与Fmoc保护缬氨酸,甘氨酸,苯丙氨酸通过DCC/DMAP耦合得标题化合物,收率95%～98%。其结构经1HNMR和MS表征。     

甘草次酸及其衍生物的研究与应用

综述了甘草次酸及其衍生物的构效关系，药理作用，作用机制与应用前景，表明了甘草次酸及其衍生物具有广泛的药理作用及开发应用前景。     

甘草黄酮的提取分离及其葡萄糖苷酶抑制活性研究

采用超声提取和碱溶酸沉法提取甘草的活性成分甘草黄酮;通过化学显色法进行定性鉴定,采用分光光度法测定甘草黄酮含量;并建立了一种基于电化学法的葡萄糖苷酶抑制活性筛选新方法,以临床降糖药阿卡波糖验证了电化学筛选法的可靠性。结果表明,甘草黄酮具有较好的葡萄糖苷酶抑制活性,其IC50为67.6mg·L~(-1)。葡萄糖苷酶抑制活性电化学筛选法具有良好的准确性和抗干扰能力,为中药葡萄糖苷酶抑制剂的研发提供了有价值的参考。     

异甘草素合成工艺优化及其清除自由基活性研究

对异甘草素的合成工艺进行优化和体外清除自由基活性进行研究。通过间苯二酚、冰醋酸、对羟基苯甲酸合成异甘草素,考察物料比、温度、反应时间对产率的影响,通过紫外分光度法对其清除自由基活性进行研究。酚与酸物料比1∶2.5,240 W微波辐射3 min,2,4-二羟基苯乙酮产率最高为65.75%;当醛酮物质的量比为3∶1,温度控制在120~130℃,回流6 h,异甘草素产率最高为28.10%;反应时间控制20 min,异甘草素加入量为1.00 m L清除DPPH自由基能力最强,为66.4%。异甘草素具有一定的抗自由基活性。     

甘草次酸差向异构体的高效液相色谱分离分析

应用整体化色谱柱,反相条件下对18H-甘草次酸差向异构体的拆分进行了探讨。采用Chromolith RP-18e整体化色谱柱,乙酸铵-乙腈-甲醇三元流动相体系,考察了乙酸铵浓度、有机添加剂含量、柱温等因素对甘草次酸差向异构体拆分的影响,在优化的色谱条件下,甘草次酸差向异构体达到了基线分离,分离度可达5.30。18α-甘草次酸与18β-甘草次酸分别在2.16~23.76μg/mL与4.24~46.64μg/mL范围内呈良好的线性关系。建立的方法简便快速,可应用于甘草次酸类药物的质量监测与控制,以及甘草次酸异构体的转化评价。     

1,7(1,5)-二芳基庚(戊)二烯类姜黄素衍生物、类似物结构与活性的关系研究

大量研究结果证明,姜黄素具有抗肿瘤,抗氧化,消炎的作用与它们的结构有密切关系,且大部分姜黄素衍生物与类似物的药理活性较姜黄素本身有所提高.这为进一步开发新的姜黄素衍生物与类似物药理功效奠定了理论基础.本文就近年来对1,7(1,5)-二芳基庚(戊)二烯类姜黄素衍生物与类似物结构的改造、修饰与其活性之间关系的研究进行探讨.     

Antimicrobial Potential of Chiral Amide Derivatives of Ricinoleic and 3-Hydroxynonanoic Acid

The growing role of fatty acid amides in medicinal chemistry has recently been observed. Therefore, using simple and fast methods, a series of chiral amide derivatives (24 compounds) of ricinoleic and 3-hydroxynonanoic acid was obtained with 31–95% yields. Then, the evaluation of their antimicrobial activity against 13 microorganisms representing Gram-positive and Gram-negative bacteria, yeast, and molds was performed. The obtained compounds showed antimold potential; however, the tested species of molds were more susceptible to derivatives of 3-hydroxynonanoic acid than to amides obtained from ricinoleic acid (RA). Interestingly, hydroxamic acids derived from RA exhibited the best activity against Candida albicans and Candida tropicalis. On the other hand, hydroxamic acids derived from 3-hydroxynonanoic acid showed the best antimicrobial potential against the remaining tested microorganisms, especially against Pseudomonas cedrina. The obtained derivatives can be considered compounds of potential pharmacological significance, which is important due to the increasing problem of microbial resistance.     

维生素C衍生物的制备及其在化妆品中的应用

维生素C衍牛物克服了维生素C易被氧化不稳定的缺点,被广泛用于化妆品中.阐述了维生素C衍生物围内外的研究情况,主要对维生素C的磷酸酯盐、糖苷、棕榈酸酯、乙基醚、甲基硅基等衍生物的制备方法进行了总结.介绍了其在化妆品中的应用情况,指出了维生素C衍生物的发展趋势.     

Development of Fibrates as Important Scaffolds in Medicinal Chemistry

Fibrates are a class of phenoxyisobutyric acid derivatives mainly used as anti-hyperlipidemic agents. The fibrate scaffold has undergone a variety of chemical modifications, providing a wide spectrum of biological activities. Within the last few years, the majority of new synthetic fibrate derivatives have demonstrated hypolipidemic activity through peroxisome proliferator-activated receptor α (PPARα) activation. However, some compounds containing the fibrate scaffold have shown different pharmacological properties, also independent of PPARα activation, such as anti-inflammatory, analgesic, antioxidant, and antiplatelet activities. The aim of this review is to highlight the structure–activity relationships (SAR) in evaluating the significance of fibrates in the field of medicinal chemistry.     

Determination of vernolic acid content in the oil ofEuphorbia lagascae by gas and supercritical fluid chromatography

Determination of the content of vernolic acid (12,13-epoxy-9c-octadecenoic) in the oil ofEuphorbia lagascae has been performed by gas chromatography of the fatty acid methyl ester derivatives of the triacylglycerols in the oil and by supercritical fluid chromatography (SFC) of the raw oil and the fatty acid derivatives of the oil. The content of vernolic acid was found to be 55 wt%. The three methods were compared, and SFC analysis of the fatty acid derivatives was found to be the most accurate method.     

Anticancer Potential of Betulonic Acid Derivatives

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.     

生物化工品乳酸及其下游产品的研究和开发

乳酸是一种重要的有机酸及生物化工品,以乳酸为原料可以得到多种衍生物,如聚乳酸、乳酸盐以及乳酸酯等。较详细地评述了乳酸的主要生产工艺和市场,介绍了几种主要的乳酸衍生物的研究和开发,比较了不同的生产路线,并展望了乳酸及其衍生物的研发方向。     

Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.     

白桦酸衍生物的抗肿瘤活性研究进展

白桦酸是一种来源于天然植物的羽扇豆烷型五环三萜类产物,具有一定的抗肿瘤活性.近年来,为了增强白桦酸的水溶性以及抗肿瘤活性,研究人员对其结构进行了大量的修饰与改造,获得了一些具有潜在抗肿瘤研究价值的白桦酸衍生物.综述了近3年来白桦酸衍生物的抗癌研究进展,以期为白桦酸的结构修饰提供帮助.     

维生素C磷酸酯衍生物的制备及其在化妆品中的应用

维生素C磷酸酯克服了维生素C易被氧化的缺点并且在化妆品中应用广泛。本文阐述了国内外研究现状,总结了化学合成和生物发酵制备维生素C磷酸酯衍生物的方法,介绍了它们在化妆品中的应用情况。指出中国应加快研发维生素C磷酸酯衍生物及其它衍生物。     

咖啡酸的合成研究

咖啡酸存在于多种中草药植物中,药理作用广泛,近年来被大量应用于临床。本文主要阐述制备咖啡酸的各种合成路线,并做简要对比评价。