3-己炔-2, 5-二醇在镍电极上电还原反应研究

采用化学计量学中新近发展的二维数据分辨方法,直观推导式演进特征投影(HELP)算法,对3-己炔-2,5-二醇在镍电极上的电还原反应得到的混合物进行了定性定量研究,得到了各组分的纯物质质谱及浓度变化曲线,且可以得到反应动力学的合理解释。说明借助化学计量学可大大扩展色质联用分析的应用范畴。     

3,7-二亚氨基-2,6-二硫杂-4,8-二氮杂双环[3,3,0]辛烷及其衍生物的合成

本文报导了3,7-二亚氨基-2,6-二硫杂-4,8-二氮杂双环[3,3,0]辛烷(5)及其衍生物四硝基(4),四乙酰基(7),二乙酰基(8)和苦味酸盐(6)的制备。(7)易失去两个乙酰基而得到二乙酰基衍生物(8),(8)还可以再乙酰化而重新得到(7)。(7)用Raney镍脱硫而得到一个直链四乙酰含氮化合物(9)。通过上述反应和有关化合物的元素分析、红外光谱、~1H核磁共振、质谱等确证了上述化合物的化学结构。     

多元曲线分辨结合在线红外用于3-氨基-4-氨基肟基呋咱的合成反应机理

利用红外光谱在线监测丙二睛、亚硝酸钠和盐酸羟胺合成3-氨基-4-氨基肟基呋咱的反应过程,采用多元曲线分辨-交替最小二乘法（MCR-ALS）、直观推导式演进特征投影法(HELP)等化学计量学方法对反应过程所获得的实时红外光谱数据矩阵进行解析,得到了各组分纯物质的浓度变化曲线和对应的红外光谱,并将多元曲线分辨 交替最小二乘法与直观推导式演进特征投影法的分析结果进行比较,得出可相互验证的一致结论,据此推出该反应合理的反应机理。 2种方法得到的反应物与生成物的光谱与原光谱的相似度近似于1,说明该解析方法具有准确性和可靠性。 结果表明,化学计量学结合红外光谱可有效的应用于3-氨基-4-氨基肟基呋咱合成过程的机理推断。     

含(1-芳乙酰胺基-2-叔胺基)乙烷结构的六氢-1H-1，4- 二氮卓类新化合物的合 成(Ⅱ)

设计并合成了2-[1-(4-(N-苯基-N-丙酰基)氨基)哌啶基]甲基-六氢-1H-1,4-二氮卓7.由3经还原、氯取代、胺取代、胺脱苄反应得到了7.7经单酰化反应得到了8.8经酰化反应后得到了11个带有(1-芳乙酰胺基-2-叔氨基)乙烷结构的六氢-1H-1,4-二氮卓类目标化合物(9a～9g,10a～10d)。     

含(1-芳乙酰胺基-2-叔胺基)乙烷结构的六氢-1H-1，4- 二氮卓类新化合物的合 成(Ⅱ)

设计并合成了2-[1-(4-(N-苯基-N-丙酰基)氨基)哌啶基]甲基-六氢-1H-1,4-二氮卓7.由3经还原、氯取代、胺取代、胺脱苄反应得到了7.7经单酰化反应得到了8.8经酰化反应后得到了11个带有(1-芳乙酰胺基-2-叔氨基)乙烷结构的六氢-1H-1,4-二氮卓类目标化合物(9a～9g,10a～10d)。     

2-芳酰氨基-5-苄基-1,3,4-噻二唑上亚甲基与4-二甲氨基苯甲醛加成反应

本文报道了2-芳酰氨基-5-苄基-1,3,4-噻二唑(1a～l)与4-二甲氨基甲醛在EtONa/EtOH体系中反应得到12种新的2-芳酰氨基-5-[1'-苯基-2'-羟基(4'-二甲氨基苯乙基)]-1,3,4-噻二唑(2a～l) .     

手性4-膦酸二酯基-3-卤-2(5H)-呋喃酮的合成与结构

手性呋喃酮1a-1b与亚磷酸三酯2a-2b通过串联的不对称Michael加成/分子内Michalis-Arbazov重排反应,得到了含磷官能团的新手性化合物,5-(S)-(l-孟氧基)-4-膦酸二酯基-3-卤素-2(5H)-呋喃酮4a-4d。该反应具有条件温和,产率高(86%-95%),光学纯度单一(d.e.≥98%)的特点。通过元素分析,IR,UV,^1HNMR,^1^3CNMR,MS,[α]~D^2^0波谱分析数据以及X射线四圆衍射数据确定了它们的化学结构和绝对构型。     

2-(N-三氟乙酰-N-三甲基硅烷基)氨基-3-三甲基硅烷氧基-羧酸三甲基硅烷酯和2-(N-三氟乙酰)-2,3-脱氢氨基酸的合成

利用三氟甲基磺酸三甲基硅烷酯, 我们合成了一种新的、化学活性很高的合成中间产物2-(N-三氟乙酰-N-三甲基硅烷基)氨基-1, 1-二(三甲基硅烷氧基)乙烯。脂肪醛或芳香醛发生碳碳成键的加成反应, 生成β碳原子上带有易离去基团三甲基硅烷氧基、N原子上带有保护基团三氟乙酰基的α氨基酸三甲基硅烷酯。消除反应得到了一个合成α、β脱氢氨基酸的可行途径。这类化合物是合成复杂多肽和肽生物碱的基元物。     

4-甲基-7，10-二氢苯并[h]香豆素的合成研究

以1-萘酚(6)为起始原料，经过Birch还原得到5，8-二氢-1-萘酚(7)；7与乙酰 乙酸乙酯在不同条件下缩合合成了4-甲基-7，10-二氢苯并[h]香豆素(4)．研究结 果表明，无氧和酸催化的反应条件对缩合反应是至关重要的．在没有酸催化的条件 下，反应生成3-乙酰基-2-羟基-6-甲基-吡喃-4-酮(8)，并通过单晶X射线衍射分析 确定了产物的结构；在酸催化的条件下，除了生成产物4外，还伴随生成脱氢芳构 化产物4-甲基苯并[h]香豆素(5)，而且在不同条件下二者的比例不同，其中以甲磺 酸为催化剂、在氮气保护下并加入抗氧化剂无水Na_2SO_3为最佳反应条件，化学选 择性约为70：30(4：5)，收率49．1％．     

[Z]-2-(芳基锡基)-1-(9-芴醇)乙烯的合成、结构与性质

用三苯基氢化锡,三对甲苯基氢化锡作为锡氢化试剂与9-乙炔基-9-芴醇进行反应,合成了2个有机锡化合物:[Z]-2-(三苯基锡基)-1-(9-芴醇)乙烯(1)和[Z]-2-(三对甲苯基锡基)-1-(9-芴醇)乙烯(2)。化合物1和2分别与ICl,Br~2,I~2反应,得到6个有机锡一卤化物,6个有机锡二卤化物和2个有机锡混合卤化物(3-16)。有机锡一碘化物7,13和有机锡二碘化物8,14与KOH乙醇溶液反应,分别得到相应的有机锡氢氧化物17,18和有机锡氧化物19,20。有机锡二碘化物8,14分别与含氮双齿配体1,10-邻菲罗啉(Phen),2,2'-联吡啶(Bipy),8-羟基喹啉(Oxin)反应,得到6个相应的配合物21-26。26个新化合物通过元素分析,锡含量测定,IR,^1HNMR测定对其结构进行了表征。同时测定了化合物2的晶体结构,晶体属单斜晶系,空间群P2~1/c。化合物2是以Sn原子为中心扭曲的四面体构型。     

基质辅助激光解吸电离飞行时间质谱研究2: 四硫 富瓦烯化合物

采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS),对四硫富瓦烯化合物进行质谱表征。在所用的实验条件下,样品很容易解吸电离生成单电荷分子离子,得到单同位素分辨的质谱图。26种实际样品的质谱分析结果表明;MALDI-TOF-MS可以比其它质谱方法更有效、更方便地用于此类化合物的质谱分析,解决了此类化合物不易进行质谱鉴定的难题。     

子窗口分析法用于偶氮染料GC-MS重叠峰的解析

 将子窗口因子分析法 (SWFA)应用于GC MS联用检测数据分析 ,并以两种偶氮染料 3,3′ 二氯联苯胺和 4,4′ 次甲基 双 (2 氯苯胺 )重叠图谱为例进行了解析。结果表明 ,此方法可直接进行目标组分的质谱分辨 ,得到目标组分的质谱图 ,进而得到该组分的色谱图。其结果准确、可靠。与窗口因子分析相比 ,子窗口的选择更加容易 ,人工干预少 ,解析速度快。     

高分辨ICP-MS测定涂料中痕量砷形态分布的研究

为建立高分辨率电感耦合等离子体质谱法(HR-ICP-MS)测定涂料中砷化合物形态分布的分析方法,应用离子交换树脂和溶剂萃取相结合的分离技术分离涂料中As(Ⅲ)、As(Ⅴ)、MMA(甲基胂酸)、DMA(二甲基胂酸)等4种砷化合物,试液直接用HR-ICP-MS法同时测定上述4种砷化合物,在高分辨质谱测量模式下避免了大量的质谱干扰,考察了采用内标元素对基体效应的校正,应用标准加入法进行定量分析,确定了实验的最佳测定条件。结果表明,方法的检出限为0.002μg/g,样品的加标回收率为98.2%～104.2%,相对标准偏差为0.72%～2.61%。该法具有简单、快速、准确等优点,应用涂料中砷化合物的4种不同形态砷的测定,结果满意。     

Characterization of a tryptic digest by high-performance displacement chromatography and mass spectrometry.

High-performance displacement chromatography (HPDC) provides a means of increasing the capacity of a chromatographic column, while maintaining the resolution afforded by high-performance liquid chromatographic (HPLC) instruments. The high capacity and high resolution of HPDC can be exploited in tryptic mapping to facilitate the characterization of a protein preparation. In this manner, minor constituents of the mixture, which may be difficult to isolate by conventional chromatographic methods, can be obtained in sufficient amounts to permit chemical characterization by established techniques. The isolation by HPDC of peptides obtained by digestion of recombinant human growth hormone (rhGH) and the subsequent characterization of the peptides are described. The identification of certain of these peptides revealed information on the specificity of trypsin for the substrate, rhGH, and for autolysis. Fractions from the HPDC tryptic map were collected and analyzed by electrospray ionization mass spectrometry (ESI-MS) either directly or following further separation by gradient elution HPLC. Fragment ions observed in the ESI mass spectra facilitated identification of peptides obtained by HPDC tryptic mapping.     

氧化钨介孔材料的制备与表征

以介孔二氧化硅(KIT-6)为硬模板, 硅钨酸为钨源, 用硬模板法制备WO3-SiO2复合材料, 再利用HF除去二氧化硅, 得到了介孔三氧化钨材料. 用X射线衍射(XRD)、能量扩散X射线(EDX)、高分辨透射电镜(HRTEM)、N2吸附-脱附等表征手段, 对制备复合材料的物料比、煅烧温度以及不同分散剂等条件进行了考察. 结果表明, 硅钨酸与硅介孔的物料比(m(WO3)/m(SiO2))在3:1到4:1之间, 在600-750 ℃下煅烧, 能制备结构较好的介孔氧化钨. 乙醇和蒸馏水为分散剂时, 用乙醇为分散剂所得的介孔WO3材料具有更高的比表面积和孔体积.     

Rapid identification of anti‐inflammatory compounds from Tongmai Yangxin Pills by liquid chromatography with high‐resolution mass spectrometry and chemometric analysis

We present an integrated approach to rapidly identify anti‐inflammatory compounds of TongmaiYangxin Pills (TMYXP), a botanical drug for the treatment of cardiovascular disease. Liquid chromatography coupled with high‐resolution mass spectrometry was used to analyze the chemical composition of TMYXP. Eighty compounds of TMYXP including flavonoids, coumarins, iridoid glycosides, saponins, and lignans, were identified unambiguously or tentatively. After the rapid isolation and bioassay, 18 fractions of TMYXP were obtained and their anti‐inflammatory activities were evaluated in lipopolysaccharide‐stimulated RAW 264.7 macrophages. We performed chemometric analysis to reveal the correlation between the chemical and pharmacological information of the fractions to facilitate the identification of active compounds. To verify the reliability of the proposed method in discovering active components from a complex mixture, activities of seven compounds, which were positively or negatively related to bioactivity according to calculation, were validated in vitro. Results indicated that six active compounds with high R values exerted certain anti‐inflammatory effects in a dose‐dependent manner with IC₅₀ values of 53.6–204.1 μM. Our findings suggest that the integrated use of identification based on high‐resolution mass spectrometry and chemometric methods could rapidly identify active compounds from complex mixture of natural products.     

Glass capillary SCOT columns by a single-step coating method

A single-step coating method for the preparation of glass capillary SCOT columns is described. It is reproducible and less time-consuming than the well-known two-step coating procedures. Other methods attempted are discussed briefly. Both the flame ionization and electron capture detectors could be used in conjunction with temperature programming. The separations achieved with an “activity mixture”, phenols and phenolic acids, illustrate the resolution obtained. The columns are suitable for quantitative determinations and a comparison is made with a conventional packed column.     

Matrix-assisted laser desorption ionization mass spectrometry with 2-(4-hydroxyphenylazo)benzoic acid matrix

A novel matrix substance, 2-(4-hydroxyphenylazo) benzoic acid, or HABA, has been found to be very advantageous for matrix-assisted ultraviolet laser desorption ionization mass spectrometry. This compound has been successfully used for the desorption of peptides, proteins, and glycoproteins up to approximately 250 kDa. For these materials, the most abundant analyte-related peaks correspond to [M + H]⁺ ions and multiply protonated molecules. Comparisons with sinapic acid, 2,5-dihydroxybenzoic acid, and α-cyano-4-hydroxycinnamic acid indicate that the new matrix provides comparable sensitivity for peptides and smaller proteins but results in better sensitivity for larger proteins and glycoproteins in protein mixtures. Other matrices discriminate against the higher mass components in these cases. Somewhat reduced mass resolution has been found for smaller proteins, but for larger proteins and glycoproteins the best mass resolution can often be obtained with the new matrix. For other classes of compounds that form ions predominantly via cation attachment, at least as good sensitivity and even better resolution have been obtained. Derivatized glycolipids and synthetic polymers have been studied in detail. For the analysis of many synthetic polymers, the best performance in terms of sensitivity and mass resolution has been observed with HABA matrix. Mass resolution was higher for cation adducts than for the protonated peptide molecules in the same mass range. The new matrix exhibits greatly extended (in time) analyte ion production and reproducibility. Owing to the uniform sample surface with this matrix, barely any spatial variation of the ion signal could be observed. In addition, many hundreds of single-shot mass spectra could be accumulated from the same spot, even for larger proteins.     

Resolution of enantiomers of the antiarrhythmic drug encainide and its major metabolites by chiral derivatization and high-performance liquid chromatography

Commercially available chiral columns were unable to provide adequate resolution of enantiomers of the antiarrhythmic drug encainide or its major metabolites. The homochiral derivatizing agent, (-)-menthyl chloroformate, was found to react at the tertiary piperidine nitrogen of racemic encainide providing two menthyl carbamate diastereomers. The individual diastereomers could be separated with baseline resolution on normal-phase high-performance liquid chromatography on a silica column. Structures of the derivatives were confirmed by electron impact mass spectrometry and 1H NMR spectroscopy. The method was adapted for the chiral analysis of the major metabolites of encainide. The limit of sensitivity for racemic encainide was 10 ng on column and it was possible to detect a mixture containing (+)- and (-)-encainide in a ratio of 1:99. Preliminary studies indicated that (-)-encainide was O-demethylated to a greater extent than the (+)-enantiomer by rat liver microsomes.     

Enhanced resolution triple-quadrupole mass spectrometry for fast quantitative bioanalysis using liquid chromatography/tandem mass spectrometry: investigations of parameters that affect ruggedness

In order to increase sample analysis throughput, the use of fast liquid chromatography in quantitative bioanalysis based on liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) has become prevalent. Therefore, it is important to increase the specificity of such bioanalytical methods. This can be done by enhancing both the chromatographic and mass resolving power. Increasing the mass spectrometric resolving power to minimize interference from endogenous compounds in the biological matrix is the subject of this paper. We present the results of our experience with developing and validating SRM-based, enhanced resolution bioanalytical methods using a new triple-quadrupole mass spectrometer with enhanced resolution capability. We have shown that SRM bioanalytical methods using better than unit-mass resolution (Q1 FWHM = 0.2 Th, Q3 FWHM = 0.7 Th) can be developed which are as rugged as unit resolution methods (Q1 FWHM = 0.7 Th, Q3 FWHM = 0.7 Th). The enhanced resolution methods require more attention to detail than unit resolution methods. For instance, the mass setting for precursor ion selection is more critical because the mass peak is narrower. Because of this, enhanced resolution methods may be more easily influenced by temperature changes in the laboratory. We have shown that there is good correlation between the shift in the precursor ion mass and the ambient temperature. Other studies carried out to investigate the effects on mass peak shape and response (both in the SIM and SRM mode) as the result of varying the FWHM revealed some interesting results. For instance, the decrease in response with the decrease in the FWHM was larger using SRM compared to that using SIM. However, the decrease in both SRM and SIM response with decreasing FWHM was significantly smaller compared with the decrease obtained using an older generation instrument. We demonstrate that, at concentrations near the limit of detection, the signal specificity can be improved by using an enhanced resolution method. To compare the performance of an enhanced resolution method against a unit resolution method under optimized mass spectrometric conditions, we analyzed calibration standards and quality control samples using a lower limit of quantitation that could be easily achieved by either method. Under these conditions, the two methods were essentially the same, demonstrating that the enhanced resolution method is as accurate, precise and rugged as the unit resolution method. We propose system suitability procedures, based on precursor ion scan, product ion scan, SRM with fractional mass changes, or SIM with a narrow scan width, for the updating of the SRM set masses before the start of analysis. We also recommend that Q1 SRM masses be determined during and at the end of analysis in order to ascertain whether or not the precursor masses have shifted during the course of the analysis.