Synthesis,Crystallographic, Quantum Chemical,Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives

In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.     

Ti(SO4)2/C催化合成硬脂酸甲酯的研究

研究了Ti(SO4)2/C在硬脂酸与甲醇酯化中的催化性能，结果表明，Ti(SO4)2/C在该反应中具有很好的催化性能，并得到了合成硬脂酸甲酯的新工艺条件；催化剂用量（硬脂酸质量分数）为5％；醇酸摩尔比为6：1，反应温度70℃，反应时间3h，优化条件，硬脂酸的酯化率达98％。     

新型3-(4-氟-苯基)-4(3H)-嘧啶酮-5-甲酸乙酯衍生物的合成

以4-氟苯基硫脲和乙氧基甲叉基丙二酸二乙酯(DEMM)为起始原料,通过环合、烷基化、氧化、水解、加成、威廉姆逊醚合成等一系列反应,合成了7个2-位具有不同取代基团的标题化合物。其结构经1HNMR、13CNMR和ESI-MS表征。     

Ti(SO4)2/SiO2催化合成丙酸异戊酯

以二氧化硅负载硫酸钛[Ti(SO4)2/SiO2]为催化剂,对丙酸和异戊醇的酯化反应进行了研究.考察了各种因素对反应的影响,确定了最佳工艺如下:醇酸物质的量比为13:1,催化剂用量为1g/0.1mol丙酸,Ti(SO4)2负载量为10%,反应温度120～135℃,反应时间60min,丙酸的酯化率可达99.6%.     

Preparation of nano - coating powder CaF2@Al(OH)3 and its application in Al2O3/Ti(C,N) self-lubricating ceramic tool materials

Nano CaF₂ particles of different sizes were prepared by direct precipitation. The diameters of nano CaF₂ particles prepared in mixed solvent can reach 5–7 nm, and can be effectively dispersed. The surface of nano CaF₂ was modified and coated by heterogeneous nucleation method. A shell layer of Al(OH)₃ was coated on the surface of nano CaF₂, and the structure and coating mechanism of the coated powder were analyzed. Under varying preparation conditions, the surface morphology of CaF₂@Al(OH)₃ was analyzed using TEM and SEM. The results showed that the coating powder showed good dispersion in mixed solvents, and the particle size of the composite powder was about 20 nm. Self-lubricating ceramic tool materials were prepared by adding coating particles to the Al₂O₃/Ti(C,N) matrix. The coating powder shell and the matrix material melt during sintering, so that CaF₂ forms nanostructures in the particles. thereby improving the mechanical properties of the material. Cutting experiments show that the addition of coating particles can effectively reduce the temperature, cutting force and friction coefficient in the cutting process of the tool, thus improving the cutting performance of the tool material.     

二氧化硅负载硫酸钛催化合成苯甲酸正丁酯

以二氧化硅负载硫酸钛[Ti(SO4)2/SiO2]为催化剂,通过苯甲酸和正丁醇反应合成了苯甲酸正丁酯,研究了醇酸物质的量比、催化剂用量、反应时间等对酯化率的影响。实验结果表明:Ti(SO4)／SiO2是合成苯甲酸正丁酯的良好催化剂,在醇酸物质的量比为3:1,催化剂用量为2.5g／0.05mol苯甲酸,反应时间为2h的条件下,苯甲酸正丁酯的酯化率可达96.1％。     

头孢托罗活性硫酯的合成工艺研究

优化了头孢托罗活性硫酯-(Z)-2-(5-氨基-1,2,4-噻二唑-3-基)-2-三苯甲氧亚胺基硫代乙酸(S-2-苯并噻唑)酯(2)的合成工艺。以3-氨基-5-乙酰胺基异噁唑(3)为原料,与特戊酰基异硫氰酸酯经重排反应,制得N-乙酰基-2-(5-特戊酰胺基-1,2,4-噻二唑-3-基)乙酰胺(5),收率为72%;采用亚硝酸异丙酯对中间体5进行肟化、然后与三苯基氯甲烷进行醚化制得(Z)-N-乙酰基-2-(5-特戊酰胺基-1,2,4-噻二唑-3-基)-2-三苯甲氧亚胺基乙酰胺(7a),收率为78%;7a经碱性水解,制得(Z)-2-(5-氨基-1,2,4-噻二唑-3-基)-2-三苯甲氧亚胺基乙酸(8),收率为65%;,在乙腈与甲苯的混合溶剂中,8与亚磷酸三乙酯、二苯并噻唑二硫醚混合反应,制得活性硫酯2,路线的总收率达24%。该合成工艺具有反应条件温和,操作简便,易于分离等优点,因而有较好的工业化应用前景。     

新型防污剂3-(1-吲哚基)-N-(4-乙氧基丙基)丙酰胺的合成

以吲哚与N,N'-二乙基丙基二硫代二丙酰胺为原料,经迈克尔加成反应,合成了3-(1-吲哚基)-N-(4-乙氧基丙基)丙酰胺,总收率为41.6%.其结构经1HNMR和IR确认.最佳制备条件为:吲哚和氢化钠的反应摩尔比1:1.8、反应温度0℃、反应时间3 h,反应溶剂为THF(四氢呋喃).     

Synthesis,Molecular Docking,In Vitro and In Vivo Studies of Novel Dimorpholinoquinazoline-Based Potential Inhibitors of PI3K/Akt/mTOR Pathway

A (series) range of potential dimorpholinoquinazoline-based inhibitors of the PI3K/Akt/mTOR cascade was synthesized. Several compounds exhibited cytotoxicity towards a panel of cancer cell lines in the low and sub-micromolar range. Compound 7c with the highest activity and moderate selectivity towards MCF7 cells which express the mutant type of PI3K was also tested for the ability to inhibit PI3K-(signaling pathway) downstream effectors and associated proteins. Compound 7c inhibited the phosphorylation of Akt, mTOR, and S6K at 125–250 nM. It also triggered PARP1 cleavage, ROS production, and cell death via several mechanisms. Inhibition of PI3Kα was observed at a concentration of 7b 50 µM and of 7c 500 µM and higher, that can indicate minority PI3Kα as a target among other kinases in the titled cascade for 7c. In vivo studies demonstrated an inhibition of tumor growth in the colorectal tumor model. According to the docking studies, the replacement of the triazine core in gedatolisib (8) by a quinazoline fragment, and incorporation of a (hetero)aromatic unit connected with the carbamide group via a flexible spacer, can result in more selective inhibition of the PI3Kα isoform.     

4-苄基-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]吗啉-3-酮的不对称转化的动态动力学拆分

以4-苄基-2-羟基吗啉-3-酮为原料,经两步反应制备得到一对非对映异构体4-苄基-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]吗啉-3-酮,然后以叔丁醇钾为碱环境,利用不对称转化的动态动力学拆分,转化为手性纯(R)-4-苄基-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]吗啉-3-酮。转化后手性产物与非对映异构体的比例为96∶4,在工业化制备神经激肽-1(NK-1)受体阻滞剂阿瑞吡坦过程中有较好的应用价值。     

固体电解质包覆LiMn2O4正极材料的合成及表征

采用湿化学法制备Li1.3Al0.3Ti1.7(PO4)3包覆LiMn2O4。采用X射线衍射、扫描电镜、恒电流充放电等技术对合成产物进行物相、形貌和电化学分析。结果表明:Li1.3Al0.3Ti1.7(PO4)3包覆LiMn2O4与LiMn2O4有相似的X射线衍射结果,且包覆后的LiMn2O4循环伏安峰电流和电荷转移阻抗变化不大。室温及55℃,以0.2 C充放电倍率循环40次时,Li1.3Al0.3Ti1.7(PO4)3包覆LiMn2O4的容量保持率分别为98.2%和93.7%,未包覆的LiMn2O4的容量保持率分别为85.4%和79.1%。当以2 C倍率室温充放电循环时,Li1.3Al0.3Ti1.7(PO4)3包覆LiMn2O4的容量保持率比未包覆的LiMn2O4高8%;55℃充放电循环时,Li1.3Al0.3Ti1.7(PO4)3包覆LiMn2O4的容量保持率比未包覆的LiMn2O4高11.1%。     

Fe2(SO4)3/膨润土固体酸催化剂催化萘异丙基化反应

通过对膨润土酸化处理得到活性白土,以活性白土为载体浸渍硫酸铁,可得到Fe2（SO4）3／膨润土固体酸催化剂：以Fe2（SO4）3/膨润土为催化剂,通过正交试验对萘的异丙基化反应工艺条件进行了考察,得到适宜的反应条件为：n（萘）／n（异丙醇）：1．8,n（萘）／n（十氢萘）=7．5,反应温度为260℃,反应时间为6h,催化剂用量为萘质量的12.5％,并各因素影响萘异丙基化反应结果进行了系统分析。此外,还对催化剂的酸强度、酸度和酸的类型进行了表征。     

地瑞那韦中间体4-氨基-N-((2R,3S)-3-氨基-2-羟基-4-苯基-丁基)-N-异丁基-苯磺酰胺的制备

地瑞那韦是一种HIV新药。以1-苄基-2,3环氧正丙基-氨基甲酸叔丁酯、对硝基苯磺酰氯为起始原料合成地瑞那韦中间体4-氨基-N-((2R,3S)-3-氨基-2-羟基-4-苯基-丁基)-N-异丁基-苯磺酰胺。产物纯度可达99.6%以上,摩尔收率96%以上。     

NaHSO4/Al2O3催化合成2-（1-环己烯基）环己酮的研究

以NaHSO4/Al2O3为催化剂,环己酮为原料,催化合成2-（1-环己烯基）环己酮。实验结果表明,NaHSO4/Al2O3具有良好的催化活性,最佳工艺条件为：环己酮100 mL,催化剂NaHSO4/Al2O3 18 g,反应温度97℃,产品收率达到59.2%。     

(Ti,V)_3AlC_2/Al_2O_3复合材料的制备及力学性能

为了提高Ti_3Al C_2陶瓷的力学性能,本研究以Ti C粉、Ti粉、Al粉和V2O5粉为起始反应原料,采用原位热压技术在1350°C下反应烧结合成出了(Ti,V)_3AlC_2/Al_2O_3复合材料。利用X-射线衍射和扫描电子显微技术对合成产物的物相和微观结构进行了表征,并分析了复合材料的合成机制。最后,对(Ti,V)_3AlC_2/Al_2O_3复合材料的力学性能进行了研究。测试结果表明:(Ti_(0.92),V_(0.08))_3Al C_2/10wt%Al_2O_3复合材料具有最佳的力学性能,其硬度、断裂韧性及抗弯强度分别为5.56 GPa、12.93 MPa·m~(1/2)和435 MPa,相比于单相Ti_3Al C_2材料分别提升了60%、108%和31%。     

Li4Ti5O12/Li1.3Al0.3Ti1.7(PO4)3复合负极材料的制备及其性能*

采用溶胶-凝胶法合成Li4Ti5O12/Li1.3Al0.3Ti1.7(PO4)3复合负极材料,通过X射线衍射、扫描电子显微镜、恒电流充放电、循环伏安和电化学阻抗研究复合材料的结构、形貌及电化学性能。结果表明：溶胶-凝胶法能合成纯相Li4Ti5O12/Li1.3Al0.3Ti1.7(PO4)3复合负极材料,所合成材料颗粒均匀。与纯相Li4Ti5O12相比,引入Li1.3Al0.3Ti1.7(PO4)3的Li4Ti5O12复合负极材料具有更低的锂离子嵌入/脱出阻抗,Li1.3Al0.3Ti1.7(PO4)3质量分数为1%、2%、3%、4%、5%的Li4Ti5O12复合材料首次放电容量比纯相Li4Ti5O12分别提高了6.2%、11.8%、15.5%、8.0%和2.0%。Li1.3Al0.3Ti1.7(PO4)3质量分数为3%的Li4Ti5O12复合负极材料20次循环后每次循环容量衰减率为0.022%,循环性能最好。     

Novel Synthesis of a New Surfactant 4-((4-Bromophenyl)(dodecyl)amino)-4-Oxobutanoic Acid Containing a Benzene Ring Using a Copper Catalyst Cross-Coupling Reaction and its Properties

A new surfactant 4-((4-bromophenyl)(dodecyl)amino)-4-oxobutanoic acid with a benzene spacer was synthesized via a novel copper catalyzed cross-coupling reaction. Its structure was confirmed by FTIR, ¹H-NMR, ¹³C-NMR and HRMS; its purity was checked by HPLC. Dynamic light scattering and an atomic force microscope showed that it forms an unusual large-diameter premicellar aggregation below the CMC.     

(E)-2-(2((6-环丙基-2-(苯胺基)嘧啶-4-基氧基)甲基)苯基)-3-甲氧基丙烯酸甲酯的合成与杀菌活性

以苯胍碳酸盐和3-环丙基-3-氧代丙酸叔丁酯为原料,经环合反应制得2-苯胺基-4-羟基-6-环丙基嘧啶,再与(E)-2-(2-(氯甲基)苯基)-3-甲氧基丙烯酸甲酯反应制得标题化合物,其结构经1H NMR进行确证.生测结果表明:该化合物在25 mg/L下对水稻稻瘟病、番茄晚疫病、蔬菜灰霉病、玉米锈病、黄瓜霜霉病和黄瓜炭疽病等都具有100%的防治效果.     

Design,Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents

In this study, a series of 4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay (EC₅₀ = 11.38 ± 1.89 µM) and plaque inhibition assay (IC₅₀ = 0.23 ± 0.15 µM). G07 also exhibited significant anti-influenza virus activities against other three different influenza virus strains A/PR/8 (H1N1), A/HK/68 (H3N2) and influenza B virus. According to the result of ribonucleoprotein reconstitution assay, G07 could interact well with ribonucleoprotein with an inhibition rate of 80.65% at 100 µM. Furthermore, G07 exhibited significant activity target PA−PB1 subunit of RNA polymerase according to the PA−PB1 inhibitory activity prediction by the best pharmacophore Hypo1. In addition, G07 was well drug-likeness based on the results of Lipinski’s rule and ADMET prediction. All the results proved that 4-[(quinolin-4-yl)amino]benzamide derivatives could generate potential candidates in discovery of anti-influenza virus agents.     

Fe3O4/聚甲基丙烯酸羟乙酯改性磁性微球对Al3+的吸附

以乙二醇二甲基丙烯酸酯为交联剂,采用悬浮聚合法制备Fe3O4/聚甲基丙烯酸羟乙酯磁性微球(mPHEMA),并经改性后制得一种新型吸附剂(M-mPHEMA).采用扫描电镜、X射线衍射、元素分析等对其进行了表征,并考察了它对Al3+的吸附性能.结果表明,制备的球形磁性吸附剂粒径45～70μm,对Al3+的饱和吸附容量为428μmol/g.pH 5～7时吸附容量最大.对饮用水的测试结果表明,M-mPHEMA对Al3+的去除率达98%,高于其他离子.用1 mol/L HNO3脱附,Al3+脱附率达98.5%,吸附剂有良好的重复使用性.