A pair of mechanistically divergent multicatalytic reaction sequences has been developed consisting of nickel‐catalyzed isomerization of N‐allylcarbamates and subsequent phosphoric‐acid‐catalyzed enantioselective functionalization of the resulting intermediates. By appropriate selection of reaction partners, in situ generated imines and ene‐carbamates are mechanistically partitioned to yield opposing functionalized products. Formal α‐functionalization to give protected α‐arylamines is achieved upon enantioselective Friedel–Crafts reaction with arene nucleophiles, whereas formal β‐functionalization is achieved upon reaction with diarylimine electrophiles in an enantioselective Povarov‐[4+2] cycloaddition. 相似文献
Anterior Gradient 2 (AGR2) has recently been reported as a tumor biomarker in various cancers, i.e., breast, prostate and lung cancer. Predominantly, AGR2 exists as a homodimer via a dimerization domain (E60-K64); after it is self-dimerized, it helps FGF2 and VEGF to homo-dimerize and promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts. Up till now, no small molecule has been discovered to inhibit the AGR2–AGR2 homodimer. Therefore, the present study was performed to prepare a validated 3D structure of AGR2 by homology modeling and discover a small molecule by screening the FDA-approved drugs library on AGR2 homodimer as a target protein. Thirteen different homology models of AGR2 were generated based on different templates which were narrowed down to 5 quality models sorted by their overall Z-scores. The top homology model based on PDB ID?=?3PH9 was selected having the best Z-score and was further assessed by Verify-3D, ERRAT and RAMPAGE analysis. Structure-based virtual screening narrowed down the large library of FDA-approved drugs to ten potential AGR2–AGR2 homodimer inhibitors having FRED score lower than ? 7.8 kcal/mol in which the top 5 drugs’ binding stability was counter-validated by molecular dynamic simulation. To sum up, the present study prepared a validated 3D structure of AGR2 and, for the first time reported the discovery of 5 FDA-approved drugs to inhibit AGR2–AGR2 homodimer by using structure-based virtual screening. Moreover, the binding of the top 5 hits with AGR2 was also validated by molecular dynamic simulation.
Graphic abstract
A validated 3D structure of Anterior Gradient 2 (AGR2) was prepared by homology modeling, which was used in virtual screening of FDA-approved drugs library for the discovery of prospective inhibitors of AGR2–AGR2 homodimer.
An expression for the density of single nucleons in a heavy spherical nucleus is derived using the shell-model and matrix
ensembles. It is shown that the theoretical expression gives an excellent fit to the density of nucleons for the nucleus197Au obtained usinge-scattering data. 相似文献
Macro-cyclic ligands from adipic acid, ethylenediamine with diethyloxalate and diethylmalonate and their respective metal complexes of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) with macro cyclic ligands (LO) and (LM) L [N,N′-bis(2-aminoethyl)hexanediamide] were synthesized successfully. These metal complexes were characterized by Fourier transform infrared, ultraviolet visible spectrometry, proton nuclear magnetic resonance spectroscopy, and mass Spectrometry, CHNS and thermogravimetric analysis. The elemental analysis confirms the structures for Mn(II), Co(II) and Ni(II) complexes similar to octahedral geometry, Cu(II) complexes as a square planar geometry and Zn(II) complexes in the tetrahedral geometry. The molar conductivities of all the metal complexes were taken in 10?3 M DMSO, and values of all the metal complexes showed their electrolytic nature which indicates the presence of chloride ions. Thermal analysis supports as the metal complexes are thermally stable. The result of antimicrobial activity against various microorganisms confirms that the metal complexes are potent bactericides and fungicides than the ligand. Metal complexes of LO with Cu(II) and Zn(II) were found to be highly active against S. typhimurium than the complexes of LM.
To convert vegetable edible oils into vanaspati ghee, nickel is used as a catalyst in the hydrogenation process. A simple and fast method for the trace level determination of nickel in ghee is reported. In this work different methods were applied for the extraction of residual nickel from ghee samples. Using toluene, benzene and carbon tetrachloride as organic solvents, an acid mixture was used for the extraction of nickel. Extracted nickel was quantified with atomic absorption and colorimetric methods. Among the organic solvents, toluene proved to be the best solvent mediating a 95% extraction of nickel from ghee samples. Nickel was extracted and determined in ten different brands of ghee and in all samples its amount was well above the permissible limit of WHO (0.2 μg/g). Other metals like lead, zinc, copper, and cadmium were also determined and their concentrations were found to be much below the WHO permissible limits. 相似文献
An identity satisfied by the eigenvalues of a real-symmetric matrix and an integral representation of a determinant using Grassmann variables are used to show that the ensemble average ofS different pairs of eigenvalues of a GOE is given by (–1)S2–S–1/2(S+1/2). 相似文献
Prochlorperazine maleate reacts with 1-naphthylamine and sodium nitrite, after heating for 110 s at 80 °C to give an orange
red colour having maximum absorbance at 460 nm. The reaction is selective for prochlorperazine maleate with 0.01 mg/mL as
visual limit of quantitation and provides a basis for a new spectrophotometric determination. The colour reaction obeys Beer’s
law from 0.01 mg/10 mL to 0.33 mg/10 mL of prochlorperazine maleate and the relative standard deviation is 0.68%. The quantitative
assessment of tolerable amounts of other drugs is also studied.
Received September 22, 2000. Revision June 19, 2001 相似文献
The principles of metal‐alkaloid ion‐pair formation and liquid‐liquid extraction are applied to the development of a sensitive and convenient atomic absorption spectrophotometery (AAS) method for the indirect determination of cocaine. In an aqueous medium of 5 M hydrochloric acid, cocaine is protonated and is associated with tetrachloro ferrate (III) anion prior to its extraction into 1,2‐dichloroethane. The critical experimental variables were identified and optimized. The method is simple and reproducible with a detection limit (DL) of 0.1 ng cm?3 cocaine in water, a relative standard deviation of 0.07 (n = 12), and the calibration graph was linear up to 50 ng cm?3 cocaine. 相似文献