减肥产品中非法添加西布曲明类似物的ESI-MS/MS检测与确证

通过分析西布曲明和减肥类健康产品中未知化合物质谱图的质谱信息,由高分辨串联质谱获得裂解碎片离子的精密质量数,质谱软件给出碎片的可能组成,推测了西布曲明和未知化合物的质谱裂解途径,进而推测出该化合物的结构。并通过合成该结构的化合物,采用液相色谱-串联质谱法对样品作确证检验,证实样品中添加了新的西布曲明类似物。该实验提供了一种可用于检测和确证健康产品中非法添加合成药物未知类似物的方法。     

手性二茂铁色氨酸化合物[Fc-(CO-L-Trp-OMe)2]的合成和结构表征

由色氨酸甲酯和1,1′-二茂铁二羧酸合成了化合物1[Fc-(CO-L-Trp-OMe)₂],并对化合物1在固体和溶液中的结构进行了表征。单晶结构表明,该化合物通过2个分子内氢键,形成了规则的手性构象。通过分子间的氢键,形成了二维网状结构。对化合物1的乙腈溶液进行了CD谱的测定,结果表明,该化合物在溶液中呈现P螺旋构象。¹H NMR谱和FTIR谱也证实了该化合物在固体和溶液状态中都形成了含分子内氢键的构象。     

铁催化酮类化合物脱氧双硼化制备非末端偕二硼（英文）

报道了一种铁催化的酮类化合物的脱氧硼化反应,通过该方法制备一系列的非末端偕二硼化合物,并进一步将该方法应用到克级规模制备中.同时,以常用有机溶剂丙酮为原料制备了相应的非末端偕二硼化合物,并对该偕二硼化合物的C—B键进行选择性单官能团或双官能团化,以验证该类化合物在有机合成中的应用价值.     

1,10-邻菲啰啉-过渡金属修饰的Keggin型多酸基化合物的合成、结构及性能研究

通过水热合成方法合成了1个新的Keggin型多酸基化合物[Zn6(phen)12(PW12O40)4](1)(phen=1,10-邻菲罗啉),并通过元素分析、红外光谱和X-射线单晶衍射方法确定了该化合物的晶体结构.目标化合物展示了1个一维的链式结构,又通过氢键构筑了1个三维"雪花"形超分子结构.利用循环伏安法研究了该化合物的电化学行为,并研究了目标化合物对亚甲基蓝的光催化降解性能.     

钯催化甲酸为氢源的芳硝基化合物直接加氢和一锅法酰胺化

Pd/C催化剂实现了甲酸为氢源的芳硝基化合物的直接加氢及甲酸为氢源和羰基源的一锅法芳硝基化合物的酰胺化.在芳硝基化合物的直接加氢过程中,该体系体现了很好的催化活性,实现了对同时带有其它可还原官能团的芳硝基化合物的选择性加氢,得到较高收率的胺类化合物.同时,通过提高反应温度和增加甲酸的量,实现了芳硝基化合物的加氢和甲酰化的串联反应,该体系体现了较高的催化活性.     

羟基官能化共价有机骨架化合物的设计合成及性质

本文设计并合成了一个具有共价有机骨架微孔结构的聚三（4-苯基）硅醇化合物。该化合物是利用乌尔曼反应,三（4-溴苯基）硅醇自聚合得到的。通过MAS NMR,FTIR,SEM,PXRD对化合物结构进行了表征。并通过TGA及氮气吸附表征化合物热稳定性及孔性质。该化合物具有高热稳定性（467 ℃失重5%）,高化学稳定性,高BET比表面积（739 m2g-1）及很窄的孔径分布（1.27 nm）。     

新型硅酸锡微孔化合物的合成与表征

利用水热合成法制备了一种新型硅酸锡微孔化合物(Microporous stannosilicates), 通过XRD, SEM, ²⁹Si MAS NMR, ¹¹⁹Sn MAS NMR, IR和TG等测试手段对该硅酸锡微孔化合物进行了表征. 结果表明, 该硅酸锡微孔化合物中的Sn物种为六配位形式, 而此化合物与硅锆矿石(Litvinskite)具有相同的拓扑结构.     

硫醇化合物在银盐CTP版材上的疏水作用

本文采用线形CCD(ChargeCoupledDevice)技术、接触角等方法研究了一种长链硫醇化合物对计算机直接制版材料物理显影动力学及疏水性能的影响。结果表明,该化合物是物理显影过程的抑制剂,在显定合一的加工液中添加该化合物可以显著提高版材物理显影银区的疏水性能。同时,通过表面显微拉曼光谱进一步证明了硫醇化合物在物理显影银表面的吸附增加了版材的亲油性。     

棉酚双-4-氟苯胺席夫碱的NMR研究

本文对合成的标题化合物进行了1H NMR和13CNMR测试,证明该化合物具有酮式结构,通过饱和转移实验发现化合物中氮上的质子与DMSO-d~6中的水有快速交换,经线型分析方法计算,求得交换体系的动力学参数。     

虎眼万年青单萜内酯新成分的分离及结构鉴定

对虎眼万年青氯仿提取物进行柱层析分离,得到一种单萜内酯(Loliolide)化合物(6-羟基-4,4,7 a-三甲基-5,6,7,7 a-四氢-4H-苯并呋喃-2-酮),用红外光谱和核磁共振波谱确定了该化合物的结构,并用电喷雾多级串联质谱对化合物的裂解机理进行了研究.通过比旋光度和核磁共振氢谱确定了化合物的立体构型.     

一个含吡咯啉氮氧自由基脲的制备和分子结构

鬼桕类化合物因具有显著的抗肿瘤活性而受到化学家和药物学家的重视 [1～ 3] ,但其较大的毒副作用促使人们不断对其结构进行改造 ,以期获得活性高而毒性低的新鬼桕毒素衍生物 .我们最初将稳定氮氧自由基作为自旋标记物引入鬼桕毒素分子中 ,发现其抗癌活性高于其母体化合物 ,并且临床用药VP- 1 6[4 ,5] 毒性低于母体化合物 .用 ESR谱对自旋标记的鬼桕毒素衍生物进行药代动力学研究 [6 ] 发现 ,酰胺类鬼桕衍生物具有较强的抗癌活性 [5] .在通常的酸和胺缩合为酰胺的反应中 ,常用二环己基碳二亚胺作为缩合剂 [7] ,但产率很低 ( 1 8%～ 2 0 % …     

Design,Synthesis and Bioactivity Evaluation of Coumarin–BMT Hybrids as New Acetylcholinesterase Inhibitors

Coumarin possesses the aromatic group and showed plentiful activities, such as antioxidant, preventing asthma and antisepsis. In addition, coumarin derivatives usually possess good solubility, low cytotoxicity and excellent cell permeability. In our study, we synthesized the compound bridge methylene tacrine (BMT), which has the classical pharmacophore structure of Tacrine (THA). Based on the principle of active substructure splicing, BMT was used as a lead compound and synthesized coumarin–BMT hybrids by introducing coumarin to BMT. In this work, 21 novel hybrids of BMT and coumarin were synthesized and evaluated for their inhibitory activity on AChE. All obtained compounds present preferable inhibition. Compound 8b was the most active compound, with the value of K_i as 49.2 nM, which was higher than Galantamine (GAL) and lower than THA. The result of molecular docking showed that the highest binding free energy was −40.43 kcal/mol for compound 8b, which was an identical trend with the calculated K_i.     

Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD.     

Novel α-Aminophosphonates and α-Aminophosphonic Acids: Synthesis,Molecular Docking and Evaluation of Antifungal Activity against Scedosporium Species

The Scedosporium genus is an emerging pathogen with worldwide prevalence and high mortality rates that gives multidrug resistance to antifungals; therefore, pharmacological alternatives must be sought for the treatment of diseases caused by this fungus. In the present project, six new α-aminophosphates were synthesized by the Kabachnik–Fields multicomponent reaction by vortex agitation, and six new monohydrolyzed α-aminophosphonic acids were synthesized by an alkaline hydrolysis reaction. Antifungal activity was evaluated using the agar diffusion method as an initial screening to determine the most active compound compared to voriconazole; then it was evaluated against 23 strains of the genus Scedosporium following the M38-A2 protocol from CLSI (activity range: 648.76–700 µg/mL). Results showed that compound 5f exhibited the highest antifungal activity according to the agar diffusion method (≤1 mg/mL). Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay and it was shown that compound 5f exhibits a lower toxicity in comparison to voriconazole at the same concentration (1000 µM). A docking study was conducted afterwards, showing that the possible mechanism of action of the compound is through the inhibition of allosteric 14-α-demethylase. Taking these results as a basis, 5f is presented as a compound with attractive properties for further studies.     

Electromembrane extraction of zwitterionic compounds as acid or base: Comparison of extraction behavior at acidic and basic pHs

This study has performed on electromembrane extraction (EME) of some zwitterionic compounds based on their acidic and basic properties. High performance liquid chromatography (HPLC) equipped with UV detection was used for determination of model compounds. Cetirizine (CTZ) and mesalazine (MS) were chosen as model compounds, and each of them was extracted from acidic (as a cation) and basic (as an anion) sample solutions, separately. 1-Octanol and 2-nitrophenyl octylether (NPOE) were used as the common supported liquid membrane (SLM) solvents. EME parameters, such as extraction time, extraction voltage and pH of donor and acceptor solutions were studied in details for cationic and anionic forms of each model compound and obtained results for two ionic forms (cationic and anionic) of each compound were compared together. Results showed that zwitterionic compounds could be extracted in both cationic and anionic forms. Moreover, it was found that the extraction of anionic form of each model compound could be done in low voltages when 1-octanol was used as the SLM solvent. Results showed that charge type was not highly effective on the extraction efficiency of model compounds whereas the position of charge within the molecule was the key parameter. In optimized conditions, enrichment factors (EF) of 27–60 that corresponded to recoveries ranging from 39 to 86% were achieved.     

Kurarinone promotes TRAIL-induced apoptosis by inhibiting NF-��B-dependent cFLIP expression in HeLa cells

This study was designed to investigate the effects of the prenylated flavonoid kurarinone on TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis and its underlying mechanism. A low dose of kurarinone had no significant effect on apoptosis, but this compound markedly promoted tumor cell death through elevation of Bid cleavage, cytochrome c release and caspase activation in HeLa cells treated with TRAIL. Caspase inhibitors inhibited kurarinone-mediated cell death, which indicates that the cytotoxic effect of this compound is mediated by caspase-dependent apoptosis. The cytotoxic effect of kurarinone was not associated with expression levels of Bcl-2 and IAP family proteins, such as Bcl-2, Bcl-x_L, Bid, Bad, Bax, XIAP, cIAP-1 and cIAP-2. In addition, this compound did not regulate the death-inducing receptors DR4 and DR5. On the other hand, kurarinone significantly inhibited TRAIL-induced IKK activation, IκB degradation and nuclear translocation of NF-κB, as well as effectively suppressed cellular FLICE-inhibitory protein long form (cFLIP_L) expression. The synergistic effects of kurarinone on TRAIL-induced apoptosis were mimicked when kurarinone was replaced by the NF-κB inhibitor withaferin A or following siRNA-mediated knockdown of cFLIP_L. Moreover, cFLIP overexpression effectively antagonized kurarinone-mediated TRAIL sensitization. These data suggest that kurarinone sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-κB-dependent cFLIP expression, indicating that this compound can be used as an anti-tumor agent in combination with TRAIL.     

Design,Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines

Novel 4-amino-thieno[2,3-d]pyrimidine-6-carboxylates substituted at the second position were prepared by cyclocondensation of 2-amino-3-cyano-thiophene and aryl nitriles in an acidic medium. The design of the target compounds was based on structural optimization. The derivatives thus obtained were tested in vitro against human and mouse cell lines. The examination of the compound effects on BLAB 3T3 and MFC-10A cells showed that they are safe, making them suitable for subsequent experiments to establish their antitumor activity. The photoirritancy factor of the compounds was calculated. Using the MTT test, the antiproliferative activity to MCF-10A, MCF-7 and MDA-MB-231 cell lines was estimated. The best antiproliferative effect in respect to the MCF-7 cell line revealed compound 2 with IC₅₀ 4.3 ± 0.11 µg/mL (0.013 µM). The highest selective index with respect to MCF-7 cells was shown by compound 3 (SI = 19.3), and to MDA-MB-231 cells by compound 2 (SI = 3.7). Based on energy analysis, the most stable conformers were selected and optimized by means of density functional theory (DFT). Ligand efficiency, ligand lipophilicity efficiency and the physicochemical parameters of the target 4-amino-thienopyrimidines were determined. The data obtained indicated that the lead compound among the tested substances is compound 2.     

UMCM-1-NH2的后合成修饰及在制备β-氨基醇反应中的应用

采用后合成修饰(PSM)技术将水杨醛锚装到UMCM-1-NH₂上, 得到席夫碱功能化的多孔金属-有机骨架化合物UMCM-1-NH-Sal, 在该化合物孔道内的席夫碱N、 O原子上螯合铜离子得到UMCM-1-NH-Sal-Cu催化剂, 并用核磁共振氢谱(¹H NMR)、 X 射线衍射(PXRD)、 热重分析(TG)、 N₂ 吸附-脱附等手段对催化剂进行了表征, 将其用于催化有机胺和环氧化物的开环反应制备β-氨基醇, 结果表明该催化剂具有良好的催化效果.     

S-, S,S-, S,S,S- Und N,S-Substituierte Dienverbindungen Und Dibutadienylpiperazinverbindungen Von 2-Nitropentachlorbutadien

Nitrodiene compound 1 was stirred with allylthiol for a long time and compound 3 was obtained. Compound 1 gave bis(thio)substituted 2-nitrodiene compound 4 and tris(thio)substituted 2-nitrodiene compound 5 with 2 moles allylthiol in the presence of NaOH in ethanol. Mono(allylthio)substituted diene compound 3 gave dibutadienyl substituted piperazine compounds with piperazine 6 in CH 2 Cl 2 (or diethylether). Compound 3 gave compound 9 with compound 8 . Compounds 11a-e have been obtained from the reaction of compound 3 with compounds 10a-e . Nach langem Rühren von der Verbindung 1 mit Allylthiol entsteht die Verbindung 3 . Die Verbindung 1 liefert mit zwei Mol von Allylthiol in ethanolischer Natronlunge die bis(thio)substituierte 2-Nitrodienverbindung 4 und tris(thio)substituierte Dienverbindung 5 . Mono(allylthio)substituierte Dienverbindung 3 ergibt mit Piperazine in CH 2 Cl 2 (oder in Ether) die dibutadienylsubstituierte Piperazinverbindung 7 . Die Verbindung 3 liefert mit der Verbindung 8 die Verbindung 9 . Durch die Reaktion von der Verbindungen 10a-c wurden die Verbindungen 11a-e erhalten.     

Identification of Rotundone as an Important Contributor to the Flavor of Oak-Aged Spirits

Experiments were conducted to identify a compound responsible for a spicy, woody, incense-like odor note in oak-aged spirits. The target compound was extracted from oak wood and various oak-aged spirits and analyzed by multidimensional (heart-cut) gas chromatography–mass spectrometry–olfactometry (MD–GC–MS–O), and was unambiguously identified as the sesquiterpene ketone, 5-isopropenyl-3,8-dimethyl-3,4,5,6,7,8-hexadydro-1(2H)-azulenone (rotundone). Quantitation of the trace-level target compound was done by stable isotope dilution analysis (SIDA) in a variety of oak-aged spirits, including bourbon, rye, Tennessee whiskey, scotch, rum, and tequila. The content of rotundone was found to increase as a function of years of barrel aging for 4-, 8-, and 12-year-old bourbons obtained from the same manufacturer, thus confirming its origin to be from oak. In addition, odor-activity values (OAVs) were compared for selected potent odorants, including rotundone, in the same 4-, 8-, and 12-year-old bourbons, which indicated the relative importance of rotundone in the overall flavor of oak-aged spirits.