Cinnamamide pharmacophore for anticonvulsant activity: evidence from crystallographic studies

A number of cinnamamide derivatives possess anticonvulsant activity due to the presence of a number of important pharmacophore elements in their structures. In order to study the correlations between anticonvulsant activity and molecular structure, the crystal structures of three new cinnamamide derivatives with proven anticonvulsant activity were determined by X‐ray diffraction, namely (R,S)‐(2E)‐N‐(2‐hydroxybutyl)‐3‐phenylprop‐2‐enamide–water (3/1), C₁₃H₁₇NO₂·0.33H₂O, ( 1 ), (2E)‐N‐(1‐hydroxy‐2‐methylpropan‐2‐yl)‐3‐phenylprop‐2‐enamide, C₁₃H₁₇NO₂, ( 2 ), and (R,S)‐(2E)‐N‐(1‐hydroxy‐3‐methyl‐butan‐2‐yl)‐3‐phenylprop‐2‐enamide, C₁₄H₁₉NO₂, ( 3 ). Compound ( 1 ) crystallizes in the space group P with three molecules in the asymmetric unit, whereas compounds ( 2 ) and ( 3 ) crystallize in the space group P2₁/c with one and two molecules, respectively, in their asymmetric units. The carbonyl group of ( 2 ) is engaged in an intramolecular hydrogen bond with the hydroxy group. This type of interaction is observed for the first time in these kinds of derivatives. A disorder of the substituent at the N atom occurs in the crystal structures of ( 2 ) and ( 3 ). The crystal packing of all three structures is dominated by a network of O—H…O and N—H…O hydrogen bonds, and leads to the formation of chains and/or rings. Furthermore, the crystal structures are stabilized by numerous C—H…O contacts. We analyzed the molecular structures and intermolecular interactions in order to propose a pharmacophore model for cinnamamide derivatives.     

N,N-二甲基乙酰胺促进N-取代肉桂酰胺的合成

以肉桂酸为原料,N,N-二甲基乙酰胺（DMAc, 4 mL)为促进剂,先与SOCl₂于0 ℃反应20 min,再与芳胺于25 ℃反应3 h,合成了10个N-取代肉桂酰胺(3a～3j),产率85.8%～96.5%,其结构经¹H NMR, ¹³C NMR, IR和EI-MS确证。提出了DMAc促进反应的可能机理。     

硅胶负载的亚胺环钯催化剂的制备、表征及催化性能

利用SiO2表面硅羟基与有机硅烷作用制得氨基化SiO2,再与邻甲氧基苯甲醛反应,可得到键合在SiO2微粒表面的席夫碱配体,该配体与Li2PdCl4甲醇溶液反应得到SiO2负载的亚胺环钯催化剂.采用傅里叶变换红外光谱、X射线固体粉末衍射和X射线光电子能谱等手段对催化剂进行了表征,并用于催化碘代苯(PhI)与丙烯酰胺(AM)反应生成反式-肉桂酰胺的反应中,考察了溶剂、温度、原料比、缚酸剂及其用量、催化剂用量和反应时间对催化性能的影响,从而得到适宜的反应条件,并探讨了反应机理.     

Characterization of tropane and cinnamamide alkaloids from Scopolia tangutica by high‐performance liquid chromatography with quadrupole time‐of‐flight tandem mass spectrometry

Scopolia tangutica is a traditional Chinese medicine used for antispasmodic, anesthesia, analgesia, and sedation. Its medicinal activity is associated to alkaloid constituents, including tropane and cinnamamide types. Low content of alkaloids in plant makes them difficult to be isolated and identified. The present work developed an effective method to quickly characterize alkaloids from Scopolia tangutica by high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. Thirteen reference compounds were studied for their fragmentation pathways, including five tropane alkaloids and eight cinnamamide ones. Alkaloid constituent was analyzed by an optimized high‐performance liquid chromatography method and mass spectrometry analysis to achieve systematic characterization of alkaloids from Scopolia tangutica. As a result, 53 compounds were identified, including 21 tropane alkaloids (eight new ones), 18 caffeoyl ones (ten new ones) and 14 dicaffeoyl ones (seven new ones). It was important to provide rich information in phytochemical study and structure‐guided isolation of important compounds from this plant.     

Crystallographic studies of cinnamamide derivatives as a means of searching for anticonvulsant activity

A cinnamamide (3‐phenylprop‐2‐enamide) core is present in many pharmacologically active compounds. We report three new crystal structures of N‐substituted cinnamamide derivatives which were screened for anticonvulsant activity, namely (R ,S )‐(2E )‐N‐(2‐hydroxypropyl)‐3‐phenylprop‐2‐enamide, C₁₂H₁₅NO₂, ( 1 ), (R ,S )‐(2E )‐N‐(1‐hydroxybutan‐2‐yl)‐3‐phenylprop‐2‐enamide, C₁₃H₁₇NO₂, ( 2 ), and (2E )‐1‐(4‐hydroxypiperidin‐1‐yl)‐3‐phenylprop‐2‐en‐1‐one, C₁₄H₁₇NO₂, ( 3 ). Compounds ( 1 ) and ( 2 ) crystallize in the Pbca space group with one molecule in the asymmetric unit, whereas compound ( 3 ) crystallizes in the P 2₁/c space group with two molecules in the asymmetric unit. All the crystal structures are stabilized by intermolecular O—H…O hydrogen bonds and additionally by N—H…O hydrogen bonds in the structures of ( 1 ) and ( 2 ). The investigated compounds possess fragments that are considered as beneficial for anticonvulsant activity. The conformations of these compounds were analyzed in comparison with the characteristic features of the proposed pharmacophore model of anticonvulsants active in the maximal electroshock test, i.e. a phenyl ring or other hydrophobic unit, an electron‐donor atom and a hydrogen‐bond acceptor/donor domain. In the reported series, two calculated distances fitted the reference model, while the third did not. Structure–activity analysis suggests that anticonvulsant properties may be related to the N‐atom substituent. It is beneficial to combine an electron‐donor atom (e.g. an O atom) with an H atom in the substituent to ensure appropriate interactions with the molecular target. We analyzed the intermolecular interactions in order to find an appropriate spatial arrangement of the important features responsible for anticonvulsant activity.     

Arylation of Acrylamide and Acrylonitrile with Arenediazonium Salts Catalyzed by Palladium Acetate

In recent years, palladium catalyzed arylation of olefins, the Heck reaction, has evolved as a powerful synthetic tool for organic chemists1. Since its discovery in the early seventies2, the reaction has undergone several modifications especially with regard to solvents, catalysts and additives. As a result, today Heck reaction is the most widely used transition metal catalyzed carbon-carbon bond forming reaction in organic synthesis3. However, despite all these modifications, little atten…     

三种肉桂酰胺衍生物的制备及其与人血清白蛋白的结合

基于临床上肉桂酰胺类药物的广泛应用及优异性能, 以间羟基肉桂酸为母体, 分别与不同氨基酸反应, 设计合成了3种未见报道的肉桂酰胺类衍生物, 并用MS、IR、¹H NMR、¹³C NMR进行结构表征.采用分子对接技术和荧光光谱法、同步荧光光谱法、紫外-可见光谱法共同研究了3种衍生物分别和人血清白蛋白(HSA)相结合的机理.AutoDock对接显示, 这3种衍生物结合在HSA亚结构域ⅡA(即site Ⅰ)的疏水腔内, 维系衍生物与HSA的主要作用力为氢键和范德华力, 同时还存在着疏水作用.光谱实验结果表明, 在体外生理条件下, 衍生物都与HSA形成复合物, 对HSA内源荧光产生静态猝灭, 且对其构象产生影响.根据不同温度下的热力学函数, 确定主要作用力均是氢键和范德华力.分子对接与实验获得了一致的结果.