用组合化学建立天然产物类似物库

天然产物是药物先导化合物的重要来源.组合化学技术在天然产物的研究中起着越来越重要的作用.目前已构建并合成了许多以天然产物为模板的化合物库,为基于天然产物的药物研究开辟了广阔的空间.     

(-)-Principinol C的全合成研究

<正>天然产物全合成是有机化学中的重要研究领域,其持续不断发展为创新药物的发现提供了重要的保证.其中,约一半新发现的小分子药物都来源于天然产物及其衍生物^[1].由于天然产物结构复杂,含量稀少且难以通过分离手段来获得稳定来源,极大地限制了天然产物在药物研发中的应用.合成方法与策略的创新,对推动天然产物全合成领域的发展起着非常关键的作用.值得注意的是,利用分子内的Pauson-Khand反应在合成具有环戊烯酮骨架的天然产物中扮演着重要角色^[2].     

基于氧化[3+2]环加成反应合成二氢苯并呋喃类天然产物

二氢苯并呋喃结构单元广泛存在于生物碱及萜类等多种天然产物中,这些天然产物大多具有良好的生物活性和药用价值.因此,近年来有关具有二氢苯并呋喃环骨架的天然产物全合成工作不断涌现.综述了近十多年来氧化[3+2]环加成反应在构建二氢苯并呋喃环骨架及各类天然产物全合成方面的应用进展.     

天然产物的质谱智能解析研究

串联质谱在鉴定天然产物的分子结构方面起着重要的作用.每一类天然产物,在串联质谱中除有常规的质谱裂解方式外,通常还具有因特定骨架类型而产生的特征裂解.因此可以通过天然产物各类成分的特征质谱裂解所产生的特征碎片离子(diagnostic ions)来确认该类天然产物的结构类型,然后再由常规的裂解方式来推测其周边可能的取代基团.基于以上思路,我们设计并构建了一种天然产物质谱智能解析软件SmartMass.     

抗肿瘤活性双四氢异喹啉生物碱类似物的合成研究进展

双四氢异喹啉天然产物是一大类具有较强生物活性的家族,目前已有近百个该类天然产物被陆续报道出来.自1974年Kluepfel等发现了第一个具有抗肿瘤活性的四氢异喹啉天然产物以来,已经有近百个该类四氢异喹啉天然产物被陆续报道出来,目前这类天然产物家族中的双四氢异喹啉生物碱因其优良的生物活性和复杂的化学结构成为了生物学和有机化学研究领域的热点,并进一步推动了该类天然产物家族成员Ecteinasicdin 743 (ET-743)在欧盟成功上市,用于治疗晚期软组织瘤和卵巢癌.由于包括ET-743在内的这类双四氢异喹啉天然产物在自然界中含量极低以及化学结构复杂,使得对其化学结构的改造也引起了越来越多的关注.本文基于此,综述了近十年来这类双四氢异喹啉天然产物类似物的研究进展.     

巴西木素类天然产物的合成研究进展

巴西木素类型天然产物是从中药苏木(Caesalpinia sappan)中分离得到的一类化合物,因其独特的结构和良好的生物活性而成为合成化学家关注的焦点.目前,已有许多关于这类天然产物合成的报道.我们主要对巴西木素类型天然产物的合成研究进展进行了综述.     

活性天然产物靶标蛋白的鉴定

天然产物是创新药物的重要来源,确定活性天然产物的靶标蛋白和作用机制是新药开发的关键.在本篇综述中,对近二十年来在活性天然产物靶标鉴定领域出现的新技术和新方法进行简要的回顾和总结,通过实例重点介绍化学蛋白质组学和生物物理学方法在天然产物靶标蛋白鉴定方面的应用,讨论各种策略的优势和不足,并对其适用范围,应用前景和发展趋势作了前瞻性的展望.     

复杂天然产物全合成:化学合成与生物合成结合的策略

天然产物全合成是有机化学的重要研究方向之一,具有复杂结构和重要生理活性的天然产物及其衍生物也是药物研发的重要来源.主要介绍利用化学合成与生物合成结合的策略,实现复杂天然产物的全合成及规模制备.主要内容包括青蒿素,Spinosyn A,Myceliothernophin E和Equisetin的化学与生物合成研究.     

天然产物液体组分饱和蒸汽压间接测定实验方法

根据物理化学中的相平衡体系热力学理论设计了间接测定天然产物液体组分饱和蒸汽压数据的实验方法,采用改进的Ellis或Rose平衡釜测定不同压力下高浓度的天然产物溶液汽液平衡数据,推算不同温度下天然产物液体组分的饱和蒸汽压,回归出Antoine方程的各参数A,B,C,建立天然产物液体组分饱和蒸汽压与温度的关联式.应用该方法测定了蒎烷、对孟烷与长叶烯的饱和蒸汽压,所得结果与文献值吻合良好,为天然产物液体组分饱和蒸汽压的实验测定与关联提供了一种便捷的途径.     

南极柳珊瑚代谢物3-Furanoeudesmene的立体选择性全合成及绝对构型确定

报道了对桉烷倍半萜天然产物3-furanoeudesmene的首次全合成.从商品化手性试剂(+)-马鞭烯酮出发,以关环烯烃复分解反应及三步法呋喃环构建为关键步骤,总共八步反应实现了目标分子的立体选择性合成.通过比对合成的目标分子的旋光值与天然产物的旋光值,确定出天然产物的绝对构型.     

Liquid chromatography-tandem mass spectrometry method for identification and quantification of two biologically active polyisoprenylated benzophenones, isoxanthochymol and camboginol, in Garcinia species

A sensitive liquid chromatography/electrospray ionization tandem mass spectrometrical (LC/ESI-MS/MS) method was developed for simultaneous identification and quantification of two polyisoprenylated benzophenones, isoxanthochymol and camboginol, in the extracts of the fruit rinds, stem bark, seed and leaves of Garcinia indica and in the fruit rinds of Garcinia cambogia. The separation of isoxanthochymol and camboginol was achieved on an RP-8 column using the solvent system consisting of a mixture of acetonitrile-water (80:20) and methanol-acetic acid (99.0:1.0) as a mobile phase in a gradient elution mode. A multiple reaction monitoring (MRM) method was developed for quantification of isoxanthochymol and camboginol in the above extracts of Garcinia species. Based on a signal-to-noise ratio of 3, the limits of detection in MRM mode for isoxanthochymol and camboginol were 2.0 and 5.0 ng/mL respectively. The method was validated in terms of linearity, accuracy and precision for 6 days. The method developed was found to be useful for identification and quantification of isoxanthochymol and camboginol in the extracts of the fruit rinds, stem bark, seed and leaves of Garcinia indica and in the fruit rinds of Garcinia cambogia.     

云南山竹子中的一个新奇的苯甲酮类化合物

多异戊烯基取代的苯甲酮类化合物存在于多种藤黄科植物中, 具有多种显著的生物活性. 为了进一步发现生物活性成分, 对藤黄科藤黄属植物云南山竹子的枝条和果实进行了研究, 从中分离得到了两个多异戊烯基取代的苯甲酮类化合物, 其中一个为新化合物. 经多种波谱方法确定了两个化合物的化学结构, 一个新化合物命名为藤黄酮K, 另一个化合物为Cambogin.     

Antioxidant Properties of Garcinia Mangostana L (Mangosteen) Rind

Many diseases correlate with antioxidant deficiencies. Garcinia mangostana L rind (GMR) belong to waste product, contains xanthones which are antioxidant compounds. The aim of this study was to determine antioxidant properties of its ethanolic extract, hexane, ethylacetate, butanol, and water fractions in DPPH scavengingactivity, level of SOD and total antioxidant (TAS) compared against α-mangostin. Extract and all of these fractions had high DPPH trapping activity while α-mangostin had low activity. Level of SOD was highest in GMR water fraction while TAS level was highest in GMR ethylacetate fraction. It was concluded that GMR products had potential antioxidant properties     

Analysis of caged xanthones from the resin of Garcinia hanburyi using ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry

On-line ultra high-performance liquid chromatography (UHPLC) coupled with electrospray quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS/MS) has been developed for the analysis of a series of caged xanthones in the resin of Garcinia hanburyi. The fragmentation of protonated molecular ions for 12 known cadged xanthones was carried out using low-energy collision-induced electrospray ionization tandem mass spectrometry. It was found that Retro-Diels-Alder rearrangement occurred in the CID processes and produced the characteristic fragment ions, which are especially valuable for the identification of this class of xanthones. The fragmentation differential between some cis-, trans-isomers was uncovered. Computation methods were utilized to rationalize the observed MS behaviors. On-line UHPLC-ESI-MS/MS/MS method has proved to be rapid and efficient in that within 6min, 15 caged scaffold xanthones, including three pairs of epimers and four pairs of isomers in gamboges, were effectively separated and identified. Among them, two known, namely isogambogenin (13) and isomorellinol (14) and one likely new caged Garcinia xanthones from the Garcinia hanburyi were tentatively characterized based on the tandem mass spectra of known ones.     

Improved liquid chromatographic method for determination of organic acids in leaves, pulp, fruits, and rinds of Garcinia

An improved liquid chromatographic (LC) method was developed for determination of organic acids in leaves, pulp, fruits, and rinds of Garcinia. At present, the commonly used LC method for analysis of organic acids in Garcinia extracts uses direct application of the extracts on the column. This practice gradually reduces efficiency of the column and shortens its life. In the improved method, the interfering substances such as pigments and xanthones were effectively removed by passing the aqueous extract through an ODS cartridge. With subsequent injection on a C18 reversed-phase column, using 6.0 mM phosphoric acid as the mobile phase with a flow rate of 1.0 mL/min and UV detection at 210 nm, the organic acids were determined in the extracts. The major organic acid was (-)-hydroxycitric acid at the level of 2.5, 0.8, 3.0, and 20.1% in leaf, pulp, fresh fruit, and dried rinds, respectively. Minor quantities of hydroxycitric acid lactone, oxalic acid, and citric acid were also identified. Limits of detection and recoveries were 0.9-1.5 microg and 93.9-99.8%, respectively. This is the first report on the composition of organic acids from Garcinia pedunculata.     

A new benzophenone from the stem bark of Garcinia benthami

From the stem bark of Garcinia benthami a new benzophenone, named Salimbenzophenone, was isolated. The structure was determined by means of spectroscopic analysis.     

Elemental Analysis of Medicinal Herbs and Dietary Supplements

Selected plants used in Traditional Chinese Medicine (Garcinia cambogia, Emblica officinalis, Angelica sinensis, Schisandra sinensis, Scutellaria baicalensis, Salvia miltiorrhiza, and Ocimum sanctum), European herbs (Echinacea purpurea, Cichorium intybus, and Vitis vinifera), and supplements derived from these products were analyzed for their macroelements (K, Na, Ca, and Mg) and microelements (Zn, Cu, Cr, Se, Mn, Mo, and Fe) concentrations by wavelength-dispersion x-ray fluorescence (WD-XRF), scanning electron microscopy–energy dispersive x-ray spectrometry (SEM–EDX), ion chromatography (IC), and inductively coupled plasma–mass spectrometry (ICP–MS). In addition, relevant aspects of heavy metal toxicity are discussed.     

A novel caged-prenylxanthone from Garcinia bracteata

<正>A novel caged-prenylxanthone xanthone,neobractatin(1),was isolated from the twig of Garcinia bracteata.Its structure was elucidated by spectroscopic methods,especially 2D NMR techniques.     

Prenylated xanthones from the bark of Garcinia xanthochymus and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities

Garcinia xanthochymus has been widely used in traditional Chinese medicine for expelling worms and removing food toxins. Bioassay-guided fractionation of an EtOAc-soluble extract of G. xanthochymus stem bark led to the isolation of six new xanthones. Their structures were elucidated by spectroscopic methods, especially 2D-NMR techniques. Free-radical-scavenging activities of the isolated compounds were elucidated through DPPH method. Most of the isolated compounds showed considerable free radical scavenging activity on DPPH assay. Compound 1 exhibited effective antioxidant scavenging activity against DPPH radical with an IC?? value of 19.64 μM, and compound 6 showed the lowest activity among all the tested molecules, with an IC?? value of 66.88 μM. These findings support the notion that the plant genus Garcinia is a good source of bioactive compounds.     

Relationship between electronic structures and antiplasmodial activities of xanthone derivatives: a 2D-QSAR approach

Structural Chemistry - Malaria is an important disease causing many death in several countries of Africa and Asia. In these continents, some plants such as Garcinia cola are used to fight against...