盐酸尼非卡兰的合成

以N，N′-二甲基脲为原料，经氰乙酸环合、乙醇胺脱氨、二氯亚砜氯化3步反应合成了关键中间体6-(2-氯乙基)胺基-1，3-二甲基-嘧啶二酮(7)。7再与：N-(2-羟乙基)-3-(4-硝基苯基)丙胺反应得抗心律失常药盐酸尼非卡兰，总收率为48．0％(以N，N′-二甲基脲计)，其结构经NMR和MS确认。     

N-丁基-4-[乙基-(3-甲基苯基)氨基]丁酰胺的合成

以γ-丁内酯为起始原料,经开环氯化和酰化反应制得N-丁基-4-氯丁酰胺(2);2与N-乙基间甲苯胺经N-烷基化反应合成了N-丁基-4-[乙基-(3-甲基苯基)氨基]丁酰胺,总收率74.6%,纯度97.6%,其结构经1H NMR和MS(ESI)确证。     

香豆素类Schiff碱的合成

以乙酸和哌啶为催化剂,在正丁醇中通过4-(N,N-二乙氨基)水杨醛与硝基乙酸乙酯的缩合反应合成了3-硝基-7-(N,N-二乙基)香豆素(2);2经SnCl2/HCl还原制得3-氨基-7-(N,N-二乙基)香豆素(3);3与芳香醛反应合成了六个新的香豆素类Schiff碱,其结构经UV,1H NMR和MS表征.     

新型1,4,5,8-萘酰亚胺类衍生物的合成

以1,4,5,8-萘四甲酸二酐(1)和2-乙基己胺(2)为原料,设计并合成了3种新型的1,4,5,8-萘酰亚胺类衍生物,其结构经1H NMR,IR和MS表征。中间体N-(2-乙基己基)-萘-1,8-二甲酸单酐-4,5-单甲酰亚胺的最佳反应条件为:19.7 mmol,n(1)∶n(2)=1.1∶1.0,以醋酸锌为催化剂,在DMF(20 mL)中于140℃反应15h,收率25%。     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应（英文）

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%～83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经¹H NMR, ¹³C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-((N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-((N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-((N-2,2-二氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%~83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经1H NMR,13C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-(N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-(N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-(N-2,2-二.氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

O-对甲氧基苯基-N,N-二苄基酪氨酸乙酯的合成

N,N-二苄基酪氨酸乙酯(2)与对溴苯甲醚(3)经偶联反应合成了O-对甲氧基苯基-N,N-二苄基酪氨酸乙酯,其结构经NMR,IR和MS表征。最佳反应条件为:210mmol,n(2)∶n(3)∶n(K3PO4)∶n(CuSO4.5H2O∶n(N,N-二甲基甘氨酸盐酸盐)=1.0∶1.3∶1.3∶0.2∶0.35,在DMF(50mL)中于100℃反应8h,产率54.7%,93.8%ee。     

芳基偶氮染料的高效合成

以4-硝基苯胺为原料,经重氮化反应后与2,5-二甲氧基苯胺偶联得芳基偶氮中间体2,5-二甲氧基-4-[(4-硝基苯基)二氮烯基]苯胺(3),3与亚硝酸异戊酯(4)重氮化后与N,N-二羟乙基苯胺(5)偶联合成了芳基二偶氮染料(6),其结构经1H NMR和13C NMR表征。考察了催化剂三氯乙酸和4用量及反应温度对6收率的影响。较优的反应条件为:以乙醇为溶剂,三氯乙酸为催化剂,三氯乙酸30 mmol,3 30 mmol,n(三氯乙酸)∶n(4)=1.0∶1.5,于0℃反应6 h,收率72%。     

乙二胺四乙酸为核的新型树枝状聚酰胺-胺的合成

采用扩散法,以乙二胺四乙酸为起始核,乙二胺和甲基丙烯酸甲酯(MMA)为原料,经重复酰胺化和Michael加成反应合成了一系列新型的树枝状聚酰胺-胺大分子(G0.5,G1.0和G1.5),其结构经1H NMR和IR表征。合成G0.5和G1.5的最佳原料配比分别为1∶24和1∶40。合成G1.0的最佳反应条件为:G0.5 12.829mmol,n(G0.5)∶n(MMA)=1∶16,于40℃反应24 h,产率85.7%。     

一种制备黄色聚氨酯弹性膜专用着色剂的合成与应用

以氯苯为原料,采用混酸硝化得到单硝基氯苯(邻-、对-混合物不经分离),在n(单硝基氯苯)∶n(硝酸)∶n(硫酸)=1.00∶1.10～1.15∶2.20及(100±5)℃下,反应65～75 min合成2,4-二硝基氯苯;然后在乙酸乙酯介质中,将得到的2,4-二硝基氯苯在n(2,4-二硝基氯苯)∶n(二乙醇胺)=1.00∶2.20及65～70℃下,与二乙醇胺进行亲核取代反应4 h,合成N,N-二(β-羟乙基)-2,4-二硝基苯胺;利用熔点测试、红外、核磁共振等技术手段确认了合成产品的化学结构。将最终产物以一定比例和其它二元醇混合,并与二异氰酸酯反应得到一种黄色聚氨酯弹性膜。通过膜强度、色迁移、耐酸碱洗涤等实验发现,设计合成的N,N-二(β-羟乙基)-2,4-二硝基苯胺的应用性能优于日本、韩国相应的反应型着色剂,完全达到美国米尔肯公司的反应型着色剂应用性能。     

含芳香基的乙二胺四乙酸酰胺衍生物的合成

乙二胺四乙酸二酐(1)与氨基芳香酸(2)进行酰化反应,合成了3种新型含芳香基的乙二胺四乙酸酰胺衍生物,其结构经UV,1H NMR,IR和元素分析表征。探讨了反应条件对收率的影响,在最佳反应条件[110mmol,n(1)∶n(2)=1∶2,pH 3~4时,于40℃反应12 h]下,收率高于75%。     

Can radical cations of the constituents of nucleic acids be formed in the gas phase using ternary transition metal complexes?

Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) of ternary transition metal complexes of [M(L(3))(N)](2+) (where M = copper(II) or platinum(II); L(3) = diethylenetriamine (dien) or 2,2':6',2'-terpyridine (tpy); N = the nucleobases: adenine, guanine, thymine and cytosine; the nucleosides: 2'deoxyadenosine, 2'deoxyguanosine, 2'deoxythymine, 2'deoxycytidine; the nucleotides: 2'deoxyadenosine 5'-monophosphate, 2'deoxyguanosine 5'-monophosphate, 2'deoxythymine 5'-monophosphate, 2'deoxycytidine 5'-monophosphate) was examined as a means of forming radical cations of the constituents of nucleic acids in the gas phase. In general, sufficient quantities of the ternary complexes [M(L(3))(N)](2+) could be formed for MS/MS studies by subjecting methanolic solutions of mixtures of a metal salt [M(L(3))X(2)] (where M = Cu(II) or Pt(II); L(3) = dien or tpy; X = Cl or NO(3)) and N to ESI. The only exceptions were thymine and its derivatives, which failed to form sufficient abundances of [M(L(3))(N)](2+) ions when: (a) M = Pt(II) and L(3) = dien or tpy; (b) M = Cu(II) and L(3) = dien. In some instances higher oligomeric complexes were formed; e.g., [Pt(tpy)(dG)(n)](2+) (n = 1-13). Each of the ternary complexes [M(L(3))(N)](2+) was mass-selected and then subjected to collision-induced dissociation (CID) in a quadrupole ion trap. The types of fragmentation reactions observed for these complexes depend on the nature of all three components (metal, auxiliary ligand and nucleic acid constituent) and can be classified into: (i) a redox reaction which results in the formation of the radical cation of the nucleic acid constituent, N(+.); (ii) loss of the nucleic acid constituent in its protonated form; and (iii) fragmentation of the nucleic acid constituent. Only the copper complexes yielded radical cations of the nucleic acid constituent, with [Cu(tpy)(N)](2+) being the preferred complex due to suppression, in this case, of the loss of the nucleobase in its protonated form. The yields of the radical cations of the nucleobases from the copper complexes follow the order of their ionization potentials (IPs): G (lowest IP) > A > C > T (highest IP). Sufficient yields of the radical cations of each of the nucleobases allowed their CID reactions (in MS(3) experiments) to be compared to their even-electron counterparts.     

离子液体中纳米铜催化Huisgen-Click反应

在绿色溶剂离子液体中,经纳米铜催化叠氮化合物和炔烃反应合成了10个1,2,3-三氮唑化合物,其结构经¹H NMR, ¹³C NMR和MS(ESI)确证。研究了催化剂、原料摩尔比、催化剂用量、反应温度和反应时间对产率的影响。结果表明：以1-丁基-3-甲基咪唑六氟磷酸盐为溶剂,n(叠氮苯) :n(苯乙炔)=1.0 :1.2,于60 ℃反应1 h,收率高达95%。     

十八烷基超支化有机物的合成

以十八胺、丙烯酸甲酯为原料,甲醇为溶剂通过迈克尔加成反应制备了0.5G(Generation)超支化有机物,再以0.5G为原料与乙二胺通过酰胺化缩合反应制备了1.0G超支化有机物.并对1.0G进行了合成条件探索,最佳反应条件为n(乙二胺)∶n(0.5G)=60∶1,反应温度60℃,反应时间24 h,产物的产率为99.11%,同时采用红外光谱对两种超支化分子进行了结构表征.     

盐酸普拉克索的合成工艺改进

以(S)-2,6-二氨基-4,5,6,7-四氢苯并噻唑（3）为原料,经缩合、还原反应制得普拉克索（2）; 2与盐酸成盐后制得盐酸普拉克索一水合物（1）,其结构经¹H NMR, ¹³C NMR, IR和MS（ESI）确证。研究了溶剂、反应温度、投料比γ［n(3) : n(正丙醛)］、析晶终止温度和精制降温速度对1收率的影响。结果表明：在最佳反应条件（无水甲醇为溶剂,γ=1.0 : 1.8,于-15~-20 ℃反应,析晶终止温度为-5~-10 ℃）下,最高收率可达61.5%。     

Photooxidation of glycated and non‐glycated phosphatidylethanolamines monitored by mass spectrometry

Phosphatidylethanolamines (PE) are one of the major components of cells membranes, namely in skin and in retina, that are continuously exposed to solar UV radiation being major targets of photooxidation damage. In addition, due to the presence of the free amine group, PE can also undergo glycation, in hyperglycemic conditions which may increase the susceptibility to oxidation. The aim of this study is to develop a model, based on mass spectrometry (MS) analysis, to identify photooxidative degradation of selected PE (POPE: PE 16:0/18:1, PLPE: PE 16:0/18:2, PAPE: PE 16:0/20:4) and glycated PEs due to UV irradiation. Photooxidation products were analysed by electrospray ionization MS (ESI‐MS) and tandem MS (ESI‐MS/MS) in positive and negative mode. Emphasis is placed in the influence of glycation in the generation of distinct photooxidation products. ESI‐MS spectra of PE after UV photo‐irradiation showed mainly hydroperoxy derivatives, due to oxidation of unsaturated fatty acyl chains. Glycated PE gave rise to several new photooxidation products formed due to oxidative cleavages of the glucose moiety, namely between C1 and C2, C2 and C3, and C5 and C6 of this sugar unit. These new products were identified by ESI‐MS/MS in positive mode showing distinct neutral loss depending on the different structure of the polar head group. These new identified advanced glycated photooxidation products may have a deleterious role in the etiology of diabetic retinopathy and in diabetic retinal microvascular complications. Copyright © 2013 John Wiley & Sons, Ltd.     

高效液相色谱-离子阱质谱法测定人血浆中的头孢拉定和青霉素G

目前,β-内酰胺类抗生素在临床抗感染药物中占有十分突出的地位,但在近年来的药品不良反应报告中,抗生素类药物引起的不良反应也占据了很高的比例,其中有我国生活环境影响、感染性疾病多的客观因素,但病人用药盲目性大、医生用药随意性多的问题也普遍存在。因此,进一步加强对抗生素类药物的监测,开发快速有效的分析测试方法显得十分重要。本文基于实际全血未知样品,开发了基于固相萃取及液质联用技术,快速准确地对血液中青霉素G及头孢拉定进行定性及质谱定量分析的检测方法。     

邻三甲氧基苯类化合物的选择性去甲基化反应研究

以溴化氢为催化剂,冰醋酸为溶剂,邻三甲氧基苯类化合物（1a~1f）为原料,于室温经选择性去甲基化反应合成了一系列丁香酸衍生物,其结构经¹H NMR和MS(ESI)确证。以丁香酸（2a）的合成为例,优化了合成条件。结果表明：在最佳反应条件(1 1 mmol, 33%HBr 0.35 mL,冰醋酸0.5 mL,于室温反应24 h)下,2收率58%~85%。2a的放大合成收率为75%。     

Negative electrospray, ion trap multistage mass spectrometry of synthetic fragments of the O-PS of Vibrio cholerae O:1

Saccharides (mono through hexasaccharides) that mimic the terminal epitopes of O-antigens of Vibrio cholerae O:1, serotypes Ogawa and Inaba, were studied by electrospray ion trap (ESI IT) mass spectrometry (MS) in the negative mode. Anionized adducts are the characteristic ions formed by the capture of H(3)O(2)(-) under the condition of ESI MS analysis. The reactive species are produced by reaction of hydroxyl anions with the molecule of water. Thus the [M + H(3)O(2)](-) have the highest m/z value in the ESI IT negative mass spectra. After dissociation of adducts by loss of 2H(2)O the [M-H](-) ions are produced. The fragmentation pathways were confirmed by multistage measurements (MS(n)). The predominant pathway of fragmentation of the mono- and oligomers is the elimination of a molecule of alpha- hydroxy--gammabutyrolactone from the 4-(3-deoxy-L-glycero-tetronamido) group. The other characteristic pathway occurs by shortening the length of oligosaccharides. In this way, conversion of the Ogawa to Inaba fragments takes place under the conditions of measurement. Negative ESI MS/MS provided sufficient information about molecular mass, the number of saccharide residues, basic structure of saccharides, about the tetronamide part of the compounds investigated and allowed Ogawa and Inaba serotypes to be distinguished.     

Separation and characterisation of sphingoceramides by high-performance liquid chromatography-electrospray ionisation mass spectrometry

We developed a simple and reliable analytical method for the quantification and the characterization of ceramides extracted from biological samples by high-performance liquid chromatography (HPLC) coupled to electrospray ionisation tandem mass spectrometry (ESI/MS/MS). The chromatographic separation of analytes was carried out in a RP8 column, eluting with a methanol-water mixture in gradient elution mode. The separated lipids were detected by total ion monitoring and characterised by MS/MS spectra; quantitative analysis was performed by integrating the extracted ion peaks obtained in the negative ion mode. Good repeatability was obtained for retention time (0.3-2%), peak area ratio (A(S)/A(IS), 2-8%), as well as limit of detection (LOD, 5-26 pg) and quantification (LOQ, 13-53 pg). The method was validated for the analysis of N-palmitoyl-D-erythro-sphingosine (Cer16), N-stearoyl-D-erythro-sphingosine (Cer18), N-tetracosanoyl-D-erythro-sphingosine (N24:0, lignoceric ceramide, Cer24:0), and N-tetracos-15'-enoyl-D-erythro-sphingosine (N24:1, nervonic ceramide, Cer24:1), giving good results. Lipid mixtures, extracted from skin and epidermal cells, were analysed for their content of the studied ceramides.