百部酰胺的全合成研究进展

百部酰胺(Stemoamide)是从百部科植物对叶百部Stemona tuberosa L.根部分离得到的天然产物。百部化合物在中医药应用中具有镇咳和驱虫的功效。其结构是γ-丁内酯并氮杂薁环的三环体系,有四个连续的手性中心。文章综述了目前国内外对百部酰胺Stemoamide的全合成方法,着重从成环顺序的角度进行论述,介绍了(Diels-Alder)-(逆-Diels-Alder)策略、自由基环化、RCM环化、分子内的Barbier反应和仿生亚胺离子环化等方法在百部酰胺全合成中的应用。     

A sensitive and selective liquid chromatography−tandem mass spectrometry method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. in rat plasma and its application to a pharmacokinetic study

Chelidonium majus L. is one of the most important medicinal plants of the family Papaveraceae. Its pharmacological effects have been primarily attributed to the presence of a number of alkaloids. In the present study, a sensitive and selective liquid chromatography?tandem mass spectrometry method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. was developed and validated. The analytes (protopine, chelidonine, coptisine, sanguinarine and chelerythrine), together with the internal standard (palmatine), were extracted from acidified rat plasma with ethyl acetate?dichloromethane (4:1, v/v). Chromatographic separation was carried out on a Diamonsil C₁₈ column with an isocratic mobile phase consisting of acetonitrile and water (adjusted to pH 2.3 with formic acid) (30:70, v/v) at a flow rate of 0.4 ml/min. Mass spectrometric detection was performed by selected reaction monitoring mode via electrospray ionization source operating in positive ionization mode. The assay exhibited good linearity (r ≥ 0.9933) for all the analytes. The lower limits of quantification were 0.197?1.27 ng/ml using only 50 µl of plasma sample. The intra‐ and inter‐day precisions were less than 11.9%, and the accuracy was between ?6.3% and 9.3%. The method was successfully applied to the pharmacokinetic study of the five alkaloids in rats after intragastric administration of Chelidonium majus L. extract. Copyright © 2013 John Wiley & Sons, Ltd.     

Simultaneous determination of three alkaloids,four ginsenosides and limonin in the plasma of normal and headache rats after oral administration of Wu‐Zhu‐Yu decoction by a novel ultra fast liquid chromatography‐tandem mass spectrometry method: application to a comparative pharmacokinetics and ethological study

A novel, sensitive and reliable ultra fast liquid chromatography‐tandem mass spectrometry (UFLC‐MS/MS) method has been developed and validated for simultaneous quantitation of eight main active ingredients (evodiamine, rutaecarpine, dehydroevodiamine, limonin, ginsenoside Rb₁, Rd, Re and Rg₁) in rat plasma after oral administration of Wu‐Zhu‐Yu (WZY) decoction, which is a celebrated and widely used Traditional Chinese Medicine formula for the treatment of headache. The analytes and internal standard (IS) were separated on a SHIM‐PACK XR‐ODS II column, and the detection was performed on a UFLC‐MS/MS system with turbo ion spray source. The lower limits of quantification were 1.5, 0.5, 1.0, 2.0, 2.0, 1.0, 0.5 and 0.2 ng ml^?1 for evodiamine, rutaecarpine, dehydroevodiamine, limonin, gensenoside Rb₁, Rd, Re and Rg₁, respectively. Linearity, accuracy, precision and absolute recoveries of the eight analytes were all within satisfaction. The IS‐normalized matrix factor was adopted for assessing the matrix effect and accompanied with a satisfactory result. The validated method has been successfully applied to compare pharmacokinetic profiles of the eight active ingredients in rat plasma between normal and headache rats after administration. Exact pharmaceutical effect of WZY decoction on headache was demonstrated by the ethological response of headache rats induced by nitric oxide donor after administration. The results indicated that the absorption of evodiamine, rutaecarpine, gensenoside Rb₁, Re and Rg₁ in headache group were significantly higher than those in normal group with similar concentration–time curves while no significant differences existed in limonin and ginsenoside Rd between the two groups. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,structure, and bonding of the hexagonal form of the oxide carbide ScAlOC

Red single crystals of a hexagonal form of ScAlOC were obtained as a by-product from the synthesis of ScAl₃C₃ by reacting scandium and carbon in an aluminium melt at 1820 °C. The crystal structure (hP8, space group P6₃mc, Z = 2, a = 3.24793(3) Å, c = 10.1739(1) Å, 629 refl., 15 param., R₁(F) = 0.010, wR₂(F²) = 0.023) can directly be derived from the binary nitrides AlN and ScN or the oxide carbides Sc(O,C) and Al(O,C), respectively. ScAlOC-II or h-ScAlOC represents a new structure type with simple closest packing of alternating layers of oxygen and carbon. The stacking sequence is ABAC (=(hc)₂) with oxygen in a cubic and carbon in a hexagonal sequence. According to the difference in size Sc occupies octahedral voids between every second layer leading to layers of edge-sharing ScO₃C₃ octahedra. Aluminium is located in half of the tetrahedral voids. The AlOC₃-tetrahedra are connected to layers by common corners of the carbon atoms. h-ScAlOC continues the row of the rare examples of oxide carbides with ordered anion distribution. Band structure calculations by FP-(L)APW methods revealed that ScAlOC is electron precise with a band gap of 1.2 eV. Calculations of charges by the Bader-method reveal values of Sc^+1.87, Al^+2.33, O^−1.52 and C^−2.67. Together with the charge densities and the values of the Laplacian this stands for a mainly ionic bonding containing significant covalent contributions, too. Despite the close similarity to rhombohedral ScAlOC (r-ScAlOC) there is a striking difference in colour, as r-ScAlOC is black. This is confirmed and explained by the results of the P-DOS, because the lowest states of the conduction band are determined by Sc-d-states. These are significantly lower in r-ScAlOC with ScC₆ and ScO₆ octahedra than in h-ScAlOC leading to a calculated band gap of 0.3 eV.     

Thermal crystallization kinetic and electrical properties of partly crystallized amorphous indium oxide thin films sputtering deposited in the presence or the absence of water vapor

Partly crystallized amorphous indium oxide thin films were deposited under water vapor atmosphere by magnetron sputtering. XRD analysis revealed that appropriate water vapor could suppress the film’s crystallinity. In situ thermal crystallization process was monitored by high-temperature XRD. The crystallization data were analyzed using the Kolmogorov–Johnson–Mehl–Avrami equation. The kinetic exponent n is determined to be approx. 1/2 and 3/2 for film deposited in the absence and the presence of water vapor, respectively. The activation energy of crystallization for film deposited under 1 × 10^?5 Torr water vapor pressure was determined to be 30.7 kJ mol^?1, which is higher than 18.9 kJ mol^?1 for film deposited in the absence of water vapor. The increased activation energy caused by the chemically bonded hydrogen and embedded O–H bonds from the water vapor resulted in the suppression of crystallization. Introduction of appropriate water vapor during the deposition decreased the resistivity because of the increase of Hall mobility. The resistivity of the films after annealing increased due to the evaporation of water vapor resulted in crystal defects.     

In vivo and in vitro metabolism of a novel β2-adrenoceptor agonist, trantinterol: metabolites isolation and identification by LC-MS/MS and NMR

Trantinterol is a novel β₂-adrenoceptor agonist used for the treatment of asthma. The aim of this study is to identify the metabolites of trantinterol using liquid chromatography tandem mass spectrometry (LC-MS/MS), to isolate the main metabolites, and confirm their structures by nuclear magnetic resonance (NMR). Urine, feces, bile, and blood samples of rats were obtained and analyzed. Reference standards of six metabolites were achieved with the combination of chemical synthesis, microbial transformation, and the model systems of rats. Moreover, in order to investigate the phase I metabolism of trantinterol in humans and to study the species differences between rats and humans, incubations with liver microsomes were performed. The biotransformation by a microbial model Cunninghamella blakesleana AS 3.970 was also studied. A total of 18 metabolites were identified in vivo and in vitro together, 13 of which were newly detected. Three phase I metabolites were detected in vivo and in vitro as well as in the microbial model, including the arylhydroxylamine (M1), the tert-butyl hydroxylated trantinterol (M2) and the 1-carbonyltrantinterol (M3). Another important pathway in rats is glutathione conjugation and further catabolism and oxidation to form consecutive derivatives (M4 through M10). Other metabolites include glucuronide, glucoside, and sulfate conjugates. The results of in vitro experiments indicate no species difference exists among rats, humans, and C. blakesleana AS 3.970 on the phase I metabolism of trantinterol. Our study provided the most comprehensive picture for trantinterol in vivo and in vitro metabolism to this day, and may predict its metabolism in humans.     

Improving the interlaminar fracture toughness of carbon fiber/epoxy composites using clustered microcapsules

The composite laminates are susceptible to delamination between reinforcing plies during their long-term service. In this paper, we propose a modified carbon fiber/epoxy composite laminate with embedded clustered dual-component microcapsules in order to increase the interlaminar fracture toughness of the lamina. The details of microcapsules were illustrated using scanning electron microscope (SEM). The modified CF/EP composite laminates were fabricated using hot-compaction technique. Mode I interlaminar fracture tests were conducted using double cantilever beam specimens, then the values of opening fracture toughness G_IC were calculated to evaluate the toughening effect of modified laminates. The toughening mechanism was revealed and discussed through micrographs of the fracture surfaces obtained by ultra-depth microscope and SEM. The results show that clustered microcapsules after polymerization are equal to special Z-pinning, significantly enhancing the ability of crack arrest, and largely and roundly improved the G_IC values of resultant composite laminates. Meanwhile, the clustered microcapsules and matrix resin formed a second-phase material layer, which also absorbed the fracture energy and suppressed the expansion of cracks.     

Statistical morphological identification of low-dimensional nanomaterials by using TEM

Nanomaterials with low-dimensional morphology display unique properties in catalysis and related fields, which are highly dependent on the structure and aspect ratio. Thus, accurate identification of the structure and morphology is the basis to correlate to the performance. However, the widely adopted techniques such as XRD is incapable to precise identify the aspect ratio of low-dimensional nanomaterials, not even to quantify the morphological uniformity with statistical deviation value. Herein, ZnO nanorod and nanosheet featured with one- and two-dimensional morphology were selected as model materials, which were prepared by the hydrothermal method and statistically characterized by transmission electron microscopy (TEM). The results indicate that ZnO nanorods and nanosheets display rod-like and orthohexagnal morphology, which mainly encapsulated with {100} and {001} planes, respectively. The 7.36 ± 0.20 and 0.39 ± 0.02 aspect ratio (c/a) of ZnO nanorods and nanosheets could be obtained through the integration of the (100) and (002) diffraction rings in selected area electron diffraction (SAED). TEM combining with the SAED is favorable compare with XRD, which not only provides more accurate aspect ratio results with standard deviation values but also requires very small amounts of sample. This work is supposed to provide a convenient and accurate method for the characterization of nanomaterials with low-dimensional morphology through TEM.     

Two Phaeophytin Type Analogues from Marine Sponge Dysidea sp.

A new compound named 13b (S)-hydroxy-17c-ethoxypheaophorbide a (2) together with a known compound 17c-ethoxypheaophorbide a (1) were isolated from marine sponge Dysidea spcollected in South China sea. The structures were elucidated by spectroscopic analysis as well as comparison with those reported in literatures.