CuCl-catalyzed Oxidative N-Demethylation of Arylamines with tButyl Hydroperoxide

CuCl-catalyzed oxidative N-demethylation of arylamines proceeded in the presence of tert-butyl hydroperoxide. The one-electron transfer route of oxidative N-demethylation competed favorably with the H-atom abstraction route.

Two Dehydroabietic Acid-based Arylamines: Synthesis, Crystal Structure and Fluorescent Properties

Two dehydroabietic acid-based arylamines have been synthesized and characterized by FTIR, 1H NMR, 13C NMR, MS spectra and elemental analysis. Their spatial structures were determined by X-ray diffraction analysis. UV-Vis absorption and fluorescence spectral characteristics of these compounds in methanol were investigated. Their fluorescence emission spectra in different polarity solvents were further evaluated. Fluorescent properties and structural relationship of the compounds showed that fluorescence intensity and quantum yield inversely increase with the non-coplanar degree. In addition, the solvent polarity has different effects on the fluorescence emission spectra of two compounds.

Direct asymmetric reductive amination for the synthesis of chiral β-arylamines

With the support by the National Natural Science Foundation of China,the research team led by Prof.Chang Mingxin(常明欣)at the Department of Chemistry and Chemical Engineering,Northwest A&F University,has developed a highly efficient method for the preparation of enantiomerically pureβ-arylamines,which was published in Angew Chem Int Ed(2016,55:5309—5312).

Heck Reaction of Iodoarenes with Methyl Acrylate Catalyzed by Cyclopalladated Complexes of Tertiary Arylamines Immobilized in Ionic Liquid [Bmim]^+BF_4^-

Heck reaction of iodoarenes with methyl acrylate, catalyzed by cyclopalladated complexes of tertiary arylamines, was investigated in ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ( +BF - 4). The products can be isolated conveniently from the ionic liquid-catalyst system. The catalysts could be reused for more than 10 times still with satisfactory catalytic activity.

Homocoupling of Aryl Iodides Catalyzed by Cyclopalladated Complexes of Tertiary Arylamines

Homocoupling of aryl iodides catalyzed by cyclopalladated complexes of tertiary arylamines gives symmetric biaryls with good yields in DMA or ionic liquid [Bmim]BF4. This catalytic alternative of the Ullmann reaction has proved to be sensitive to both electronic and steric factors of substrates.

Density Functional Theory Study on the Histidine-assisted Mechanism of Arylamine N-Acetyltransferase Acetylation

Arylamine N-acetyltransferases （NATs, EC 2.3.1.5） catalyze the N-acetylation of primary arylamines, and play a key role in the biotransformation and metabolism of drugs, carcinogens, etc. In this paper, three possible reaction mechanisms are investigated and the results indicate that if the acetyl group directly transfers from the donor to the acceptor, the high activation energies will make it hard to obtain the target products. When using histidine to mediate the acetylation process, these energies will drop in the 15-45 kJ/mol range. If the histidine residue is protonated, the corresponding energies will be decreased by about 35-87 kJ/mol. The calculations predict an enzymatic acetylation mechanism that undergoes a thiolate-imidazolium pair, which agrees with the experimental results very well.

Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes

Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, Cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.

A pilot study of the modulation of sirtuins on arylamine N-acetyltransferase 1 and 2 enzymatic activity

Arylamine N-acetyltransferase(NAT; E.C. 2.3.1.5) enzymes are responsible for the biotransformation of several arylamine and hydrazine drugs by acetylation. In this process, the acetyl group transferred to the acceptor substrate produces NAT deacetylation and, in consequence, it is susceptible of degradation. Sirtuins are protein deacetylases, dependent on nicotine adenine dinucleotide,which perform post-translational modifications on cytosolic proteins. To explore possible sirtuin participation in the enzymatic activity of arylamine NATs, the expression levels of NAT1, NAT2,SIRT1 and SIRT6 in peripheral blood mononuclear cells(PBMC) from healthy subjects were examined by flow cytometry and Western blot. The in situ activity of the sirtuins on NAT enzymatic activity was analyzed by HPLC, in the presence or absence of an agonist(resveratrol) and inhibitor(nicotinamide) of sirtuins. We detected a higher percentage of positive cells for NAT2 in comparison with NAT1, and higher numbers of SIRT1t cells compared to SIRT6 in lymphocytes. In situ NAT2 activity in the presence of NAM inhibitors was higher than in the presence of its substrate, but not in the presence ofresveratrol. In contrast, the activity of NAT1 was not affected by sirtuins. These results showed that NAT2 activity might be modified by sirtuins.

Probing the architecture of the Mycobacterium marinum arylamine N-acetyltransferase active site

Treatment of latent tuberculosis infection remains an important goal of global TB eradication.To this end,targets that are essential for intracellular survival of Mycobacterium tuberculosis are particularly attractive.Arylamine N-acetyltransferase(NAT)represents such a target as it is,along with the enzymes encoded by the associated gene cluster,essential for mycobacterial survival inside macrophages and involved in cholesterol degradation.Cholesterol is likely to be the fuel for M.tuberculosis inside macrophages.Deleting the nat gene and inhibiting the NAT enzyme prevents survival of the microorganism in macrophages and induces cell wall alterations,rendering the mycobacterium sensitive to antibiotics to which it is normally resistant.To date,NAT from M.marinum(MMNAT)is considered the best available model for NAT from M.tuberculosis(TBNAT).The enzyme catalyses the acetylation and propionylation of arylamines and hydrazines.Hydralazine is a good acetyl and propionyl acceptor for both MMNAT and TBNAT.The MMNAT structure has been solved to 2.1Åresolution following crystallisation in the presence of hydralazine and is compared to available NAT structures.From the mode of ligand binding,features of the binding pocket can be identified,which point to a novel mechanism for the acetylation reaction that results in a 3-methyltriazolo[3,4-a]phthalazine ring compound as product.

Microwave-assisted convenient synthesis of N-arylpyrrolidines in water

An efficient and clean synthesis of N-arylpyrrolidines from arylamines and 1,4-dimesyloxybutane was developed using microwave irradiation in an aqueous potassium carbonate medium without any catalyst.The procedure is rapid,simple and convenient.

Synthesis of P,N-2,2'-biphenyl derivatives with central chirality

Enantiopure 2-(dicyclohexylphosphino)-1,1'-biphenyl derivatives substituted in the 2'-position by a chiral amino group were prepared.For the compound bearing an acyclic chiral chain,the key step was a Suzuki coupling between bromobenzeneboronic acid and N-Boc-iodoaniline whereas an aromatic nucleophilic substitution allowed the introduction of a chiral pyrrolidine in the 2'-position of the biphenyl backbone.The efficiency of the P,N-biphenyl pyrrolidine derivatives as ligands in Pd-catalyzed arylaminations compares well with that of DavePhos ligand.

What a Role did Histidine Residue Play in Arylamine N-Acetyltransferase 2 Acetylation？ A Quantum Chemistry Study

Arylamine N-acetyltransferases （NATs, EC 2.3.1.5） catalyze an acetyl group transfer from acetyl coenzyme A （AcCoA） to primary arylamines and play a very important role in the metabolism and bioactivation of drugs and carcinogens. Experiments revealed that His-107 was likely the residues responsible for mediating acetyl transfer. The full catalytic mechanism of acetylation process has been examined by density functional theory. The results indicate that, if the acetyl group is directly transferred from the donor, p-nitrophenyl acetate, to the acceptor, cysteine, the high activation energy will be a great hindrance. These energies have dropped in a little range of 20-25 kJ/mol when His-107 assisted the transfer process. However, when protonated His-107 mediated the reaction, the activation energies have been dropped about 73-85 kJ/mol. Our calculations strongly supported an enzyme acetylation mechanism that experiences a thiolate-imidazolium pair, and verified the presumption from experiments.