三萜类化合物Bardoxolone methyl对急性呼吸窘迫综合征大鼠氧化应激信号通路Nrf2-ARE/HO-1的影响

目的观察三萜类化合物Bardoxolone methyl(BARD)对急性呼吸窘迫综合征(ARDS)大鼠氧化应激信号通路核转录因子相关因子2(Nrf2-ARE)/血红素氧合酶-1(HO-1)的影响。方法100只大鼠按随机数字法分为药物BARD组及生理盐水组,喂养一周后两组按是否建立ARDS模型再各分为两亚组,产生四组:ARDS模型+BARD干预组(A1组),ARDS模型+生理盐水组(A2组),正常+BARD干预组(B1组),正常+生理盐水组(B2组)。各组大鼠再喂养72h后处死留取肺组织及血液标本。病理观察肺组织结构变化。免疫组织化学检测肺组织Nrf2、HO-1蛋白表达情况。反转录-多聚酶链反应(RT-PCR)检测肺组织Nrf2 mRNA、HO-1 mRNA表达情况。结果肺组织病理结构变化:A2组肺组织损伤程度最重,病理评分最高。其次A1组,B1及B2组结构大致正常。Nrf2、HO-1蛋白表达情况:A1组(3.78±0.37,2.86±0.16)及B1组(3.01±0.34,2.47±0.19)高于A2(1.82±0.31,2.01±0.21)及B2组(0.92±0.13,1.41±0.17),A1组高于B1组,A2组高于B2组(P均<0.05)。Nrf2mRNA、HO-1mRNA表达情况:A1组(2.16±0.17,1.45±0.12)最为明显,B1组(1.79±0.14,1.18±0.05)高于B2组(0.42±0.06,0.68±0.11),A2组(1.18±0.19,1.01±0.07)高于B2组(0.42±0.06,0.68±0.11,P均<0.05)。结论三萜类化合物Bardoxolone methyl能够明显上调肺组织Nrf2-ARE/HO-1信号通路相关蛋白的表达,从而发挥抗氧化应激作用,减轻ARDS时肺组织的损伤。

UPLC-PDA快速检测即食性蔬菜中氯虫苯甲酰胺、甲基硫菌灵和多菌灵残留

残留分析物从含0.1%乙酸的乙腈溶液中提取,提取液用适量C18、PSA和NANO进行基质分散萃取净化,以Waters ACQUITY UPLC BEH C18柱为分离分析柱,以乙腈和水为色谱流动相梯度洗脱,以254 nm为紫外检测波长,建立叶菜(生菜)、瓜菜(黄瓜)和果菜(西红柿)中氯虫苯甲酰胺、甲基硫菌灵和多菌灵残留的QuEChERS样品前处理程序和UPLC-PDA分析方法.检测方法的性能指标验证结果显示,优化色谱条件下,0.01 mg/L~5 mg/L质量浓度的三种目标分析物在UPLC-PDA上均有良好的线性响应;在三种样品基质中设定的三种目标分析物在三个添加水平下的回收率分别为76%~115%,相对标准偏差均小于10%;三种蔬菜中三种农药的检测限均低于0.05 mg/kg.总体来看,该QuEChERS样品前处理程序简单、高效、可靠、节省有机溶剂;优化的UPLC-PDA分析方法快速、灵敏、可靠,可以用于三种即食性蔬菜中氯虫苯甲酰胺、甲基硫菌灵和多菌灵的残留量检测.

Synthesis,Crystal Structure and Fungicidal Activity of(E)-2-[(4-tert-Butyl-5-(4-methoxybenzyl)thiazol-2-ylimino)methyl]phenol

The title compound （E）-2-[（4-tert-butyl-5-（4-methoxybenzyl）thiazol-2-ylimino）methyl]phenol was synthesized by the reaction of 5-（4-methoxybenzyl）-4-tert- butylthiazol-2-amine with salicylaldehyde, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, space group P21/c with a = 5.9362（8）, b = 11.5070（15）, c = 29.460（4）A, β= 97.326（3）°, V = 1995.9（5） A^3, Z = 4, F（000） = 808, C22H24N2O2S, Mr= 380.49, De= 1.266 g/cm^3, S = 1.031,μ = 0.181 mm^-1, the final R = 0.0474 and wR = 0.1441 for 4327 observed reflections （I 〉 2σ（I））. Intramolecular O-H…N hydrogen bond is observed in the crystal. The preliminary bioassay showed that the title compound exhibits 95% inhibition rate against Rhizoctonia solani at the test concentration of 500 mg/L.

Synthesis and Crystal Structure of 4-(4,6-dimethoxyl -pyrimidin-2-yl)-3-thiourea Carboxylic Acid Methyl Ester

The title compound 4-（4,6-dimethoxylpyrimidin-2-yl）-3-thiourea carboxylic acid methyl ester was synthesized by the reaction of 2-amino-4,6-dimethoxyl pyrimidine, potassium thiocyanate and methyl chloroformate in ethyl acetate. Single crystals suitable for X-ray measurement were obtained by recrystallization with the solvent of dimethyl formamide at the room temperature. The structure was characterized by elemental analysis and IR and determined by X-ray diffraction analysis＇ Crystallographic data： C9H12N4O4S, Mr = 272.29, monoclinic, space group C2/m with a = 1.6672（3）, b = 0.66383（12）, c = 1.1617（2） nm, β = 109.275（2）°, V = 1.2136（4） nm^3, Dc = 1.490 g/cm^3,μ = 0.281 mm^-1, F（000） = 568, Z = 4, R1 = 0.0341and wR2 = 0.1042.

Synthesis and Crystal Structure of (Z)-Methyl-3-methoxy-2-{2-[(4-(E-3-p-tolylacryloyl)phenoxy)methyl]phenyl}acrylate

The title compound,（Z）-methyl-3-methoxy-2-{2-[（4-（E-3-p-tolylacryloyl）phenoxy）-methyl]phenyl}acrylate,was synthesized and determined by X-ray single-crystal diffraction. The crystal belongs to the triclinic system,space group P1 with a = 8.0157（8）,b = 12.5748（13）,c = 13.3768（14） ,α = 64.770（2）,β = 75.720 （2）,γ = 89.784（2）°,μ = 0.085 mm-1,Mr = 442.49,V = 1174.1（2） 3,Z = 2,Dc = 1.252 g/cm3,F（000） = 468,T = 294（2） K,R = 0.0603 and wR = 0.1498 for 2644 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that the single crystal contains strong non-classical hydrogen bonds. The preliminary bioassay showed that the title compound exhibits inhibitory activity against the Pseudoperoniospora cubensis and Rhizoctonia solani at the test concentration of 200 mg/L.

Synthesis, Structure and Quantum Mechanical Calculations of Methyl 2-(5-((Quinolin-8-yloxy)-methyl)-1,3,4-oxadiazol-2-ylthio)-acetate

The title compound was synthesized by the base catalyzed reaction of 5-（（quinolin- 8-yloxy）methyl）-1,3,4-oxadiazole-2（3H）-thione with methyl chloroacetate. The structure was supported by the spectroscopic data and unambiguously confirmed by single-crystal X-ray diffraction studies. It crystallizes from a methanol solution in the triclinic space group Pi with unit cell dimensions a = 7.4509（9）, b = 10.2389（12）, c = 12.2299（15）A, a = 74.771（2）, β = 77.956（2）, 7 = 69.263（2）°, V = 834.98（17） A3 and Z = 2. In order to gain some valuable insights into the molecular structure, the quantum mechanical calculations were performed using both HF and time-dependent density functional theory at the B3LYP/6-31G（d,p） level. The molecular geometry from X-ray determination of the title compound in the ground state has been compared using the Hartree-Fock （HF） and density functional theory （DFT） with the 6-31G（d） basis set. The calculated results show that the DFT and HF can well reproduce the structure of the title compound. The energetic behavior of the title compound was examined using the B3LYP method with the 6-31G（d） basis set. The harmonic vibrational frequencies calculated have been compared with the experimental FTIR and FT-Raman spectra. The restricted Hartree-Fock and density functional theory-based nuclear magnetic resonance （NMR） calculation procedure was also performed, and it was used for assigning the 13C and 1H NMR chemical shifts of the title compound. Moreover, molecular electrostatic potential and thermodynamic parameters of the title compound were investigated by theoretical calculations.

Stereoselective Synthesis of (+)-△~5-Dehydrosugiyl Methyl Ether

A stereoselective synthetic route to △~5-dehydrosugiyl methyl ether was developed from (S)-(-)-α-cyclocitral, DDQ as a better oxidant for enone was used.

Synthesis and Crystal Structure of Methyl 3-(5-Bromo-1-ethyl-1H-indole-3-carbonyl)aminopropionate

Methyl 3-（5-bromo-l-ethyl-lH-indole-3-carbonyl）aminopropionate has been synthesized by the acylation of 5-bromo-3-trichloroacetylindole with β-alanine methyl ester, followed by alkylation with ethyl iodide, in 82.6% yield. Its crystal structure was gotten and determined by X-ray diffraction method. The crystal is of monoclinic, space group P2/c with a = 11.7927（8）, b = 14.9342（8）, c = 9.0060（5） A, β = 101.558（6）°, V = 1553.93（16） A3, Z = 4, Dc= 1.510 g/cm3, 2 = 0.71073 A,μ（MoKa） = 2.656 mm-1, Mr = 353.22 and F（000） = 720. The structure was refined to R = 0.0401 and wR = 0.0825 for 1704 observed reflections with I 〉 2σ（I）. In the crystal structure, intermolecular N（2）-H（2）...O（1） hydrogen bond and weak intermolecular bonds （C（1）-H（1）...O（1） and C（10）-H（10B）-O（2）） are formed, and π-π stacking also exists.

Synthesis and Crystal Structure of Methyl 2-(Diphenylamino)-4-phenyl-1,3-thiazole-5-carboxylate

The title compound, methyl 2-（diphenylamino）-4-phenyl-1,3-thiazole-5-carboxylate, was synthesized and studied by single-crystal X-ray diffraction method. The structure of the product was confirmed by IR, 1H- and 13C-NMR spectroscopy and elemental analysis. These experimental studies were supported by quantum mechanical calculations. The structure was solved in monoclinic, space group P21/c with a = 9.573（3）, b = 19.533（7）, c = 9.876（3）, β = 92.35（4）°, V = 1845.2（10）3, T = 85（2） K, Z = 4, R = 0.040 and wR = 0.089 for 6424 observed reflections with I2σ（I）.

HELIX SENSE-SELECTIVE COPOLYMERIZATION OF TRIPHENYLMETHYL METHACRYLATE WITH CHIRAL ANIONIC INITIATORS

Optically active copolymers of pairs of three monomers, triphenyl (methyl methacrylate)and one or two pyridyl substituted methyl methacrylate homologues, were obtained by helix-sense-selective copolymerization using complexes of organolithium with chiral ligand as anionicinitiators in toluene at low temperature. The copolymers obtained with (-)-sparteine (Sp) and(S,S)-(+)-and (R, R)-(-)-2, 3-dimethoxy-1, 4-bis (dimethylamino) butanes((+)-and (-)-DDB) complexes of organolithium showed low optical activity, but PMP complex with N, N-diphenylethyleneamine monolithium amide (PMP-DPEDA-Li) was effective in synthesizingcopolymers of high optical rotation ([α]_D^(25) about+320～1370°)which were comparable to thoseof relative homopolymers with one-handed helical structure.

Syntheses and Crystal Structures of Methyl 2-(4,5-Dibromo-1-methylpyrrole-2-carbonylamino)-3-phenylpropanoate and 4,5-Dibromo-1-methyl-2- trichloroacetylpyrrole

4,5-Dibromo-1-methyl-2-trichloroacetylpyrrole Ⅰ, prepared by the reaction of 1-methyl-2-trichloroacetylpyrrole with Br2 in 98.6 % yield, was condensed with methyl L-2-amino-3- phenylpropanoate to afford methyl 2-（4,5-dibromo-1-methylpyrrole-2-carboxmido）-3-phenylpropanoate Ⅱ in 90.8% yield. Crystal data for Ⅰ： monoclinic system, space group P21/c with a = 8.595（3）, b = 10.900（4）, c = 12.321（5） ,A°,β = 92.292（7）°, V = 1153.4（8）A°^3, Dc = 2.213 g/cm^3, F（000） = 728, CTH4Br2Cl3NO, Mr = 384.28, λ = 0.71073 A°, μ（MoKa） = 7.688 mm^-1, Z = 4, R = 0.0338 and wR2 = 0.0840 for 1963 observed reflections with I 〉 2a（I）. Crystal data for Ⅱ： monoclinic system, space group P21 with a = 4.886（2）, b = 15.921（8）, c = 11.635（6） A°,β = 101.803（9）°, V = 885.9（7） A°^3, Dc = 1.665 g/cm^3, F（000） = 440, C16H16Br2N2O3, Mr = 444.13, λ = 0.71073 A°, μ（MoKa） = 4.590 mm^-1, Z = 2, R = 0.0335 and wR2 = 0.0837 for 3191 observed reflections with I 〉 2σ（I）. The crystal structure reveals that compound Ⅱ forms the one-dimensional chain structure via the intermolecular hydrogen bonds of N（2）-H…O（1）.

Systematic pharmacology analysis of Sodium 8-(((carboxymethyl)amino)methyl)-4',7-bishydroxy-isoflavone-3'-sulfonate

The purpose of this study is to use the newly synthesized molecule Sodium 8-(((carboxymethyl)amino)methyl)-4',7-bishydroxy-isoflavone-3'-sulfonate(M)as a research object,the pharmacological mechanism of the molecule was analyzed by using a series of Systematic pharmacology methods.The results show that the M molecule has a higher drug-like DL value of 0.59 and better molecular property parameters,namely Hdon=4,Hacc=10 and AlogP=0.94;A total of 11 M molecules related targets,namely F2,ESR1,AR,F10,CA2,DPP4,CCNA2,PRSS1,CDK2,GSK3B and PTPN1;A total of 140 diseases are associated with M molecule targets,and these diseases are mainly related to cancer and cardiovascular diseases;A total of 52 pathways involve the pharmacological mechanisms of M molecules,which are mainly related to cancer and other related diseases;GO-enriched analysis showed that these targets are closely related to the regulation of peptidase activity and biological processes such as blood coagulation and hemostasis.This article clearly demonstrated the pharmacological mechanism of M molecule,which provides references for exploring the pharmacological mechanism of new compounds.

Synthesis of Intermediate N-Chloroformyl-N-[4-(trifluoromethoxy)phenyl]Methyl Carbamate of Indoxacarb

[Objective]The paper was to study a synthetic method suitable for industrial production of intermediate N-Chloroformyl-N-[4-(trifluoromethoxy)phenyl]methyl carbamate of indoxacarb.[Method]Using 4-trifluoromethoxy aniline as the starting material,[4-(trifluoromethoxy)phenyl]carbamate was synthesized by homogeneous formylation method without acid-binding agent.Subsequently,it was reacted with sodium methoxide/potassium methoxide by reactive distillation to obtain[4-(trifluoromethoxy)phenyl]carbamate ammonium sodium/potassium,then directly reacted with triphosgene to obtain crude products of N-carbonochloridoyl-N-[4-(trifluoromethoxy)phenyl]carbamate;finally,competing product was obtained by recrystallization.[Result]The intermediate N-chloroformyl-N-[4-(trifluoromethoxy)phenyl]carbamate was synthesized by the method.The content of products was higher than 98%.The yield of product reached above 96%(calculated by 4-trifluoromethoxy aniline).[Conclusion]The method used for the synthesis of intermediate N-chloroformyl-N-[4-(trifluoromethoxy)phenyl]methyl carbamate was simple,with less three wastes,higher safety and lower cost.

Synthesis and Crystal Structure of N-((6-chloropyridin-3-yl)methyl)-6-ethoxy-N-ethyl-3-nitropyridin-2-amine

The title compound N-（（6-chloropyridin-3-yl）methyl）-6-ethoxy-N-ethyl-3-nitropyri-din-2-amine（4） was synthesized by reacting the mixture of 6-chloro-2-ethoxy-3-nitropyridine（1） and 2-chloro-6-ethoxy-3-nitropyridine（2） with 3,and its structure was determined by X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group P21/n with a = 7.3441（2）,b = 9.9041（3）,c = 11.7368（3） ,α = 101.410（2）,β = 102.1340（10）,γ = 99.594（2）o,μ = 0.260 mm^-1,Mr = 336.78,V = 798.58（4）（A°）^3,Z = 2,Dc = 1.401g/cm^3,F（000） = 352,T = 296（2） K,R = 0.0210 and wR = 0.1053.

Synthesis and Crystal Structure of 1,4-Dimethyl-2,5-di{[2’-(3-pyridylmethylamino-formyl)phenoxyl]methyl}benzene Perchlorate

The title compound, 1,4-dimethyl-2,5-di { [2′-（3-pyridylmethylaminoformyl）phenoxyl]- methyl}benzene perchlorate （C36H36Cl2N4O12, Mr = 787.59）, has been synthesized and structurally determined by single-crystal X-ray diffraction. The crystal crystallizes in the orthorhombic system, space group Pbca with a = 14.366（4）, b = 15.159（4）, c = 16.443（5）A, V = 3580.9（17）/A3 Z = 4, De = 1.461 g/cm^3, /t = 0.253 mm^-1, F（000） = 1640, R = 0.0618 and wR = 0.1525 for 1615 observed reflections （I 〉 2σ（I））. In the structure of the title compound, a two-dimensional supramolecular layer is formed via intermolecular hydrogen bonding interactions.

QuEChERS-液相色谱-串联质谱法同时检测土壤和柑橘中吡唑醚菌酯、甲基硫菌灵及其代谢物多菌灵的残留

建立了QuEChERS-液相色谱-串联质谱法(LC-MS/MS)检测土壤和柑橘中吡唑醚菌酯、甲基硫菌灵及其代谢物多菌灵的分析方法。样品经甲醇或乙腈提取,N-丙基乙二胺(PSA)净化后,用液相色谱分离,电喷雾正离子多反应监测(MRM)模式进行质谱测定,以基质匹配标准溶液进行外标法定量。吡唑醚菌酯、甲基硫菌灵和多菌灵的定量限(LOQ,S/N=10)分别为5.8~7.0μg/kg、9.3~14.1μg/kg和2.1~2.6μg/kg。样品的加标回收率为75.48%~109.18%,相对标准偏差(RSD)为0.60%~5.11%(n=5)。该法快速简便,定量准确,用基质配制标准溶液能够有效、准确地校正LC-MS/MS测定吡唑醚菌酯、甲基硫菌灵和多菌灵残留的基质效应,满足土壤、橘皮、橘肉和柑橘全果实际样品的检测需求。

液相色谱-质谱法同时测定甜瓜样品中的噻菌灵、甲基托布津、扑海因

采用液相色谱 质谱法同时测定甜瓜样品中的噻菌灵、甲基托布津和扑海因含量。离子化技术采用大气压电喷雾 (+)方式 ,定量测定使用选择离子监测模式。检测离子m /z :2 0 2 .2 5、343.2 8、331 .0 7。检出限 :噻菌灵为 0 .1 pg ,甲基托布津为 1 0 .2pg ,扑海因为 2 .4 2ng ;回收率为 81 .0 %～ 1 1 0 % ;相对标准偏差为1 5 %～ 1 6 .8%。方法灵敏度高 ,选择性好 ,准确度高 ,用于甜瓜样品中噻菌灵、甲基托布津、扑海因的测定 。

TurboFlow在线净化/液相色谱-串联质谱法测定水果蔬菜中多菌灵、吡虫啉、啶虫脒与甲基硫菌灵的残留量

建立了TurboFlow在线净化/液相色谱-串联质谱同时测定水果蔬菜中多菌灵、吡虫啉、啶虫脒和甲基硫菌灵残留的方法.样品用乙腈提取,经Cyclone-p在线净化柱净化后,将富集的分析物洗脱转至Betasil Phenyl-hexyl C18分析柱,经色谱分离后,电喷雾串联质谱检测.结果表明,4种农药在1～50 ng/mL范围内呈良好线性,相关系数均大于0.999 7.方法的定量下限（LOQ）为10 μg/kg.4种农药在3个水平的加标回收率为80.3％～109.9％,相对标准偏差为1.5％ ～7.8％.

QuEChERS-高效液相色谱法测定铁皮石斛中多菌灵和甲基硫菌灵的残留量

目的:建立QuEChERS-高效液相色谱法测定不同产地铁皮石斛中多菌灵与甲基硫菌灵农药残留量的方法。方法:铁皮石斛样品用乙腈溶液提取,经QuEChERS方法净化,采用Waters C_(18)色谱柱(150 mm×4.6mm,5μm)、乙腈-0.02 mol/L乙酸铵缓冲溶液(20∶80)为流动相,流速1 mL/min、柱温35℃、检测波长280 nm,对不同产地铁皮石斛中多菌灵与甲基硫菌灵残留量进行检测。结果:多菌灵在0.05~25 mg/L范围内呈良好的线性关系,相关系数等于0.999 4,检测限为0.01 mg/kg,定量限为0.04 mg/kg,3个添加水平下的平均回收率是98.28%,RSD是2.68%;甲基硫菌灵在0.025~12.5 mg/L范围内呈良好的线性关系,相关系数等于0.999 5,检测限为0.02 mg/kg,定量限为0.06 mg/kg,3个添加水平下的平均回收率是101.03%,RSD是3.64%;50批铁皮石斛中有4批分别检出多菌灵与甲基硫菌灵农药残留,均低于《中国药典》2015年版中药有害残留物限量制定指导原则农药残留量最大限量理论值。结论:建立的QuEChERS-高效液相色谱法检测多菌灵和甲基硫菌灵,具有操作简单,高效、专属性好、重复性强、结果准确可靠等优点。

沉淀-Fenton氧化预处理甲基硫菌灵废水

研究沉淀-Fenton氧化对甲基硫菌灵生产废水的预处理,考察SCN^-和CODcr的去除效果。先加入Cu-SO4和Na2S2O3对SCN^-进行沉淀,考察CuSO4和Na2S2O3加入量对CODcr去除率的影响;对沉淀后水样进行Fenton氧化,通过改变pH值、H2O2浓度、Fe^2＋浓度、反应时间等得出该农药废水在常温下的最佳操作条件。实验结果表明,经过沉淀处理后的废水,pH值为4、H2O2投加量为6～7 g/L、Fe^2＋投加量为1.2～1.5 g/L,氧化时间为2～4 h,CODcr浓度从12 000 mg/L降至3 600 mg/L,总去除率达到了70%。