In order to improve the yield and reduce the cost in the synthesis of antitumor drug vismodegib the key intermediates are prepared and the Negishi reaction step is examined.The effects of different molar ratios of rea...In order to improve the yield and reduce the cost in the synthesis of antitumor drug vismodegib the key intermediates are prepared and the Negishi reaction step is examined.The effects of different molar ratios of reactants dosages of catalyst and time for refluxing are investigated by using single factor tests.The results demonstrate that when the molar ratios of 2-bromopyridine 2-chloro-N-4-chloro-3-iodophenyl -4-methylsulfonyl benzamide zinc chloride n-butyllithium and tetrakis triphenyl phosphine palladium are changed to 1.0∶0.5∶1.5∶1.1∶0.05 and the mixture is refluxed for 24 h the production yield is improved to 72%.This reaction condition significantly enhances the synthetic efficiency avoids consuming excessive raw materials/catalysts and meanwhile prevents a prolonged reaction time.The optimization of the proportion of reactants and the heating time is proved to be important for the efficiency and economy in cross-coupling reaction to synthesize vismodegib.展开更多
Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid （FA） ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 n...Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid （FA） ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 nanoparticles were characterized by X-ray diffraction diffractometer, transmission electron microscope, FT-IR spectrometer, vibrating sample magnetometer, and dynamic light scattering instrument. The in vivo labeling effect of folate-conjugated Fe3O4 nanoparticles on the hepatoma cells was investigated in tumor-bearing rat. The results demonstrate that the as-prepared nanoparticles have cubic structure of Fe3O4 with a particle size of about 8 nm and hydrated diameter of 25.7 nm at a saturation magnetization of 51 A·m2/kg. These nanoparticles possess good physiological stability, low cytotoxicity on human skin fibroblasts and negligible effect on Wistar rats at the concentration as high as 3 mg/kg body mass. The folate-conjugated Fe3O4 nanoparticles could be effectively mediated into the human hepatoma Bel 7402 cells through the binding of folate and folic acid receptor, enhancing the signal contrast of tumor tissue and surrounding normal tissue in MRI imaging. It is in favor of the tumor cells labeling, tracing, magnetic resonance imaging （MRI） target detection and magnetic hyperthermia.展开更多
A combinatorial approach was applied to investigating the influence of Fe content on the microstructures and properties of Ti6Al4V alloy.A diffusion couple was manufactured with Ti6Al4V and Ti6Al4V20Fe alloys and anne...A combinatorial approach was applied to investigating the influence of Fe content on the microstructures and properties of Ti6Al4V alloy.A diffusion couple was manufactured with Ti6Al4V and Ti6Al4V20Fe alloys and annealed at 1000°C for 600 h to obtain a wide range of compositions.By combining electron probe micro-analysis(EPMA),scanning electron microscopy(SEM)and nanoindentation,the relationships between composition and microstructure as well as hardness were determined.It is found that after aging the Ti6Al4V5Fe sample contains reasonable(about 55%)volume fraction of fineαphase and shows the peak hardness among the Ti6Al4VxFe alloys.Therefore,it is a promising candidate for the development of titanium alloys.HAADF-STEM and XRD reveal that after quenching from the singleβphase field,the metastableα''lamellae form in the Ti6Al4V5Fe alloy,and on subsequent isothermal aging,theα''lamellae become coarse and act as precursors/preferential nucleation sites for the stableαphase.展开更多
Ligands containing NH groups often show special characteristics.In this paper,a well-defined dinuclear Cu（II） complex bearing an unsymmetrical bipyridine-pyrazole-amine ligand was synthesized by the condensation of ...Ligands containing NH groups often show special characteristics.In this paper,a well-defined dinuclear Cu（II） complex bearing an unsymmetrical bipyridine-pyrazole-amine ligand was synthesized by the condensation of N–H to release H2O.Using sodium L-ascorbate as a reductant,the binuclear complex showed excellent activity in 1,3-dipolar cycloaddition reactions between alkynes and azides to obtain 1,4-disubstituted triazoles in 95%–99% isolated yields.展开更多
基金The National Basic Research Program of China(973Program)(No.2011CB933503)China Postdoctoral Science Foundation(No.2013M541592)
文摘In order to improve the yield and reduce the cost in the synthesis of antitumor drug vismodegib the key intermediates are prepared and the Negishi reaction step is examined.The effects of different molar ratios of reactants dosages of catalyst and time for refluxing are investigated by using single factor tests.The results demonstrate that when the molar ratios of 2-bromopyridine 2-chloro-N-4-chloro-3-iodophenyl -4-methylsulfonyl benzamide zinc chloride n-butyllithium and tetrakis triphenyl phosphine palladium are changed to 1.0∶0.5∶1.5∶1.1∶0.05 and the mixture is refluxed for 24 h the production yield is improved to 72%.This reaction condition significantly enhances the synthetic efficiency avoids consuming excessive raw materials/catalysts and meanwhile prevents a prolonged reaction time.The optimization of the proportion of reactants and the heating time is proved to be important for the efficiency and economy in cross-coupling reaction to synthesize vismodegib.
基金Project(2011JQ028)supported by the Fundamental Research Funds for the Central Universities,ChinaProjects(2008SK3114,2010SK3113)supported by Hunan Provincial Science&Technology Plan,China+2 种基金Project(B2007086)supported by Science&Research Funds of Hunan Health Department,ChinaProject(12JJ5057)supported by Natural Science Foundation of Hunan Province,ChinaProjects(XCX1119,XCX12073)supported by University Students Innovative Experiment Plan Project of Hunan Agricultural University,China
文摘Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid （FA） ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 nanoparticles were characterized by X-ray diffraction diffractometer, transmission electron microscope, FT-IR spectrometer, vibrating sample magnetometer, and dynamic light scattering instrument. The in vivo labeling effect of folate-conjugated Fe3O4 nanoparticles on the hepatoma cells was investigated in tumor-bearing rat. The results demonstrate that the as-prepared nanoparticles have cubic structure of Fe3O4 with a particle size of about 8 nm and hydrated diameter of 25.7 nm at a saturation magnetization of 51 A·m2/kg. These nanoparticles possess good physiological stability, low cytotoxicity on human skin fibroblasts and negligible effect on Wistar rats at the concentration as high as 3 mg/kg body mass. The folate-conjugated Fe3O4 nanoparticles could be effectively mediated into the human hepatoma Bel 7402 cells through the binding of folate and folic acid receptor, enhancing the signal contrast of tumor tissue and surrounding normal tissue in MRI imaging. It is in favor of the tumor cells labeling, tracing, magnetic resonance imaging （MRI） target detection and magnetic hyperthermia.
基金Project(2014CB644000)supported by the National Basic Research Program of ChinaProject(2016YFB0701301)supported by the National Key Technology R&D Program of China+1 种基金Projects(51371200,51671218)supported by the National Natural Science Foundation of ChinaProject supported by State Key Laboratory of Powder Metallurgy,Central South University,China
文摘A combinatorial approach was applied to investigating the influence of Fe content on the microstructures and properties of Ti6Al4V alloy.A diffusion couple was manufactured with Ti6Al4V and Ti6Al4V20Fe alloys and annealed at 1000°C for 600 h to obtain a wide range of compositions.By combining electron probe micro-analysis(EPMA),scanning electron microscopy(SEM)and nanoindentation,the relationships between composition and microstructure as well as hardness were determined.It is found that after aging the Ti6Al4V5Fe sample contains reasonable(about 55%)volume fraction of fineαphase and shows the peak hardness among the Ti6Al4VxFe alloys.Therefore,it is a promising candidate for the development of titanium alloys.HAADF-STEM and XRD reveal that after quenching from the singleβphase field,the metastableα''lamellae form in the Ti6Al4V5Fe alloy,and on subsequent isothermal aging,theα''lamellae become coarse and act as precursors/preferential nucleation sites for the stableαphase.
基金supported by the China Postdoctoral Science Foundation(2013M541254)the National Natural Science Foundation of China(21502120)+1 种基金the Program for Innovative Research Team of the Ministry of Educationthe Program for Liaoning Innovative Research Team in University~~
文摘Ligands containing NH groups often show special characteristics.In this paper,a well-defined dinuclear Cu（II） complex bearing an unsymmetrical bipyridine-pyrazole-amine ligand was synthesized by the condensation of N–H to release H2O.Using sodium L-ascorbate as a reductant,the binuclear complex showed excellent activity in 1,3-dipolar cycloaddition reactions between alkynes and azides to obtain 1,4-disubstituted triazoles in 95%–99% isolated yields.
