Efficient Synthesis of Quinolines via a Knoevenagel/Staudinger/aza-Wittig Sequence

A simple and efficient method for the construction of quinoline derivatives from 2-azidobenzaldehyde and various carbonyl compounds was developed. The process involves a Knoevenagel condensation of 2-azidobenzaldehyde with carbonyl compound and subsequently an intramolecular normal Staudinger/aza-Wittig reaction to form the quinolone ring in satisfactory yields.     

Polyfluorobenzoyl chlorides and isothiocyanates in reactions with CH-reactive benzimidazoles

Reactions of 2-benzoylmethylbenzimidazole with tetra- and pentafluorobenzoyl chlorides afford fluorine-containing 6-benzoyl-7H-benzimidazo[3,2-a]quinolones. 2-Cyanomethyl- or 2-benzoylmethylbenzimidazole reacts with tetra(penta) fluorobenzoyl isothiocyanates to give fluorine containing 1,3-benzothiazinones, which differently behave in reactions with cycloalkylimines.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 720–724, March, 2005.     

A Simple,Convenient One‐Pot Synthesis of Dithio‐Carbamide Derivatives of Heterocyclic 1,3‐Dicarbonyl Systems

A various new dithi‐ocarbamides were synthesized from heterocyclic six‐membered 1,3‐dicarbonyl systems, such as 4‐hydroxy‐2,5‐pyranopyridines, 4‐hydroxy‐2‐pyridones, 4‐Hydroxy‐2‐quinolones, 4‐hydroxy‐coumarins, and 4‐hydroxy‐1‐methyl‐2‐quinolones. The dicarbonyl compounds in the presence of anhydrous potassium carbonate in dimethyformamide react with tetraalkylthiuram disulfides to yield 3‐dialkylaminothiocarbonylthio derivatives through a simple, convenient one‐pot reaction. The structures were confirmed by using IR, NMR, and elemental analysis.     

Spectroscopic characterization,photoinduced processes and cytotoxic properties of substituted N‐ethyl selenadiazoloquinolones

7‐R‐9‐ethyl‐6,9‐dihydro‐6‐oxo‐[1,2,5]selenadiazolo[3,4‐h]quinolines (R = H, COOC₂H₅, COOCH₃, COOH and COCH₃, E1h , E2h , E3h , E4h , E5h ) and 6‐ethyl‐6,9‐dihydro‐9‐oxo‐[1,2,5]selenadiazolo[3,4‐f]quinoline ( E1f ) were characterized by UV/vis, FT‐IR and fluorescence spectroscopy. The electronic absorption spectra of the derivatives E1h , E2h , E3h and E5h in the aprotic solvents dimethylsulfoxide (DMSO) and acetonitrile (ACN) reveal low‐energy absorption maxima with λ_max > 400 > nm, shifted hypsochromically in water. In DMSO, N‐ethyl selenadiazoloquinolones behave as strong fluorescent agents (λ_em ≥ 550 nm) with the exception of the carboxylic acid derivative E4h which shows only poor emission. Photoinduced reactions of N‐ethyl selenadiazoloquinolones were investigated by means of electron paramagnetic resonance (EPR) spectroscopy. Photoexcitation of N‐ethyl selenadiazoloquinolones in aerated DMSO with either 385 nm or 400 nm wavelengths, monitored by EPR spin trapping technique, results in the generation of superoxide radical anions; under an inert atmosphere, the generation of methyl radicals originating from the solvent predominates. Upon exposure at either 365 nm, 385 nm or 400 nm, aerated ACN solutions of selenadiazoloquinolones in the presence of sterically hindered amines produce nitroxide radicals via a reaction with photogenerated singlet oxygen. The 7‐substituted derivatives of 9‐ethyl‐6,9‐dihydro‐6‐oxo‐[1,2,5]selenadiazolo[3,4‐h]quinoline behave as photosensitizers activating molecular oxygen upon photoexcitation and possess the sufficient photochemical stability under the given experimental conditions. The cytotoxic effects of non‐photoactivated and UVA photoactivated N‐ethyl substituted selenadiazoloquinolones on cancer (human HeLa and murine L1210) and non‐cancer (NIH‐3T3) cell lines were monitored by the MTT test. The derivative E2h demonstrates the highest cytotoxic/photocytotoxic activity on the neoplastic cell lines. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of Selected Quinolones and Fluoroquinolones by Use of TLC

Abstract

There are many different methods of quinolones determination. The most often used method of quinolones analysis is liquid chromatography. In this work some selected quinolones (cinoxacin, pipemidic acid) and fluoroquinolones (ofloxacin, pefloxacin) were separated with thin-layer chromatography (TLC). The two different mobile phases were used as follows: buffer solution (pH = 5.5)-methanol, 40:10 (v/v) and acetonitrile-water-acetic acid, 6:40:4 (v/v/v), respectively, for quinolones and fluoroquinolones. The following chromatographic parameters were calculated for these separations: R_F, ?R_F, R_M, and R_S. The possibility of qualitative determination of cinoxacin, pipemidic acid, ofloxacin, and pefloxacin using TLC was shown.     

Determination of (fluoro)quinolones in environmental water using online preconcentration with column switching linked to large sample volumes and fluorescence detection

An analytical method based on online enrichment using coupled-column liquid chromatography with fluorescence detection has been developed to determine marbofloxacin, ciprofloxacin, danofloxacin, enrofloxacin, norfloxacin, lomefloxacin, oxolinic acid, and nalidixic acid at trace levels in surface water. The sample containing the pharmaceuticals was pumped through a short C18 column in such a way that the analytes were retained on the column, whereas polar interferences, eluting at the first of the chromatogram, were discarded to waste. Then, the analytes were transferred by the chromatographic mobile phase to a second C18 analytical column, where they were separated following a conventional chromatography. The optimized approach allowed to preconcentrate 15 mL of sample volume adjusted at acid pH with phosphoric acid and modified with 5% of methanol, at a flow rate of 1.5 mL/min in 10 min. R(2) values were between 0.994 and 0.998, detection and quantitation limits ranged between 0.001 and 0.080 and between 0.002 and 0.100 μg/L, respectively, and the interday precision was below 9.8%. Recoveries in three different surface water samples, spiked at concentration levels between 0.002 and 0.500 μg/L (n = 3 for each spiking level), ranged from 82.1 to 125.8% with the relative standard deviation lower than 12%.     

液相色谱-串联质谱法同时测定化妆品中的25种喹诺酮类药物

建立了直接提取结合液相色谱-电喷雾串联质谱同时测定化妆品中丹诺沙星、恩诺沙星、氟甲喹、恶喹酸、环丙沙星、沙拉沙星、萘啶酸、诺氟沙星、氧氟沙星等25种喹诺酮类药物的方法。样品经酸性乙腈提取和正己烷脱脂净化,采用Poroshell EC-C₁₈色谱柱分离,含0.1%甲酸的乙腈-水溶液为流动相进行梯度洗脱,电喷雾串联质谱正离子模式扫描,多反应监测(MRM)模式检测,外标法定量。实验通过空白基质液配制标准溶液,以降低基质对离子化干扰造成的基质效应,25种喹诺酮类药物在1~200 mg/kg范围内线性关系良好,相关系数(r)在0.999以上。方法的检出限为1.0 mg/kg,在1、5、10 mg/kg 3个加标水平下,水、乳、霜型化妆品中加标回收率为87.4%~105%,相对标准偏差(RSD)为4.54%~19.7%(n=6)。结果表明,该方法简便、快速、准确,适用于化妆品中25种喹诺酮类药物的测定。     

超高效液相色谱-串联质谱法同时测定牛奶中38种抗生素残留

建立了超高效液相色谱-串联质谱(UPLC-MS/MS)同时测定牛奶中5类(磺胺类、喹诺酮类、四环素类、氯霉素类和大环内酯类)38种抗生素的分析方法。牛奶样品以0.5%(体积分数)甲酸乙腈提取,利用Oasis PRiME HLB固相萃取小柱进行净化,经Acquity UPLC HSS T3柱(100 mm×2.1 mm i.d.,1.8μm)分离,采用电喷雾离子源,多反应监测模式(MRM)进行定性定量分析。结果表明,38种抗生素在各自线性范围内呈良好的线性关系,相关系数(r~2)均大于0.99,定量下限为0.10～1.0μg/kg;在1.0、5.0、10.0μg/kg加标水平下,平均回收率为70.7%～94.9%,相对标准偏差(RSD,n=6)为4.0%～9.4%。该方法操作简单、灵敏度高、重现性好,适用于牛奶中多种抗生素残留的监测要求。     

高效液相色谱-串联质谱法同时测定鳗鱼和虾中残留的33种喹诺酮和磺胺类药物

建立了鳗鱼和虾中33种喹诺酮类(QNs)和磺胺类(SAs)药物残留量的高效液相色谱-串联质谱(HPLC-MS/MS)测定方法。以氘代试剂为内标,样品经酸性乙腈萃取后,用正己烷脱脂,旋转蒸发浓缩,采用LC-MS/MS选择反应监测(SRM)正离子模式测定,同时对鳗鱼和虾中的33种QNs和SAs进行定性和定量。33种QNs和SAs的检出限(S/N=3)为1.0 μg/kg,定量限(S/N=10)为2.0 μg/kg;在10.0～200.0 μg/L时目标物的峰强度与质量浓度的线性关系良好(r>0.99);平均回收率为66%～123%。该法简便快捷,降低了分析成本,也在一定程度上实现了药物残留的快速检测。     

鸡肉中11种喹诺酮类药物多残留的高效液相色谱检测

建立了用荧光检测器同时测定11种喹诺酮类药物(包括诺氟沙星、培氟沙星、环丙沙星、恩诺沙星、氧氟沙星、达氟沙星、洛美沙星、二氟沙星、沙拉沙星、恶喹酸和氟甲喹)在鸡肉中的多残留的高效液相色谱检测方法。鸡肉样品用10%三氯乙酸-乙腈(体积比为7∶3)提取两次并稀释,随后用反相固相萃取柱净化。采用Hypersil BDS-C18色谱柱分离,以乙腈和水为流动相梯度洗脱,荧光检测器用程序编程检测波长检测。11种喹诺酮类药物标准曲线的线性范围为5～1200 μg/L,相关系数大于0.998。在高、中、低三个添加水平下的回收率为56%～119%,批内相对标准偏差为0.4%～16.1%,批间相对标准偏差为1.4%～23.0%。检出限和定量限分别为1～23 μg/kg和4～40 μg/kg。该方法快速、灵敏,达到了兽药残留检测的要求。