-
Molecules (Basel, Switzerland) Jan 20197-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this...
7-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this article, we provide the first synthesis of fluorinated derivatives. Fluorination using Selectfluor of benzo[1,2,4]triazin-7-ones occurs regioselectively and in high yield at the enamine-activated position. This electron N-lone pair activation overrides the activation/deactivation effects of some other substituents. The reaction time was significantly reduced with the use of microwave irradiation at 120 °C and 7 bar. The cytotoxicity and cyclic voltammetry measurements for 8-fluoro-1,3-diphenylbenzo[][1,2,4]triazin-7(1)-one () are presented and compared with its synthetic precursor, 1,3-diphenylbenzo[][1,2,4]triazin-7(1)-one ().
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Diazonium Compounds; Halogenation; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Molecular Structure; Structure-Activity Relationship; Triazines
PubMed: 30646524
DOI: 10.3390/molecules24020282 -
Molecules (Basel, Switzerland) Aug 2018A novel series of pyrazolyl 1,3,4-thiadiazines ⁻, ⁻, , ⁻, ⁻, and was prepared from the reaction of pyrazole-1-carbothiohydrazide , with...
A novel series of pyrazolyl 1,3,4-thiadiazines ⁻, ⁻, , ⁻, ⁻, and was prepared from the reaction of pyrazole-1-carbothiohydrazide , with 2-oxo-'-arylpropanehydrazonoyl chloride, 2-chloro-2-(2-arylhydrazono)acetate, and 3-bromoacetylcoumarin. Moreover, the regioselective reaction of 5-pyrazolone-1-carbothiohydrazide with 4-substituted diazonium salts and 4-(dimethylamino)benzaldehyde gave the corresponding hydrazones ⁻ and . The newly prepared compounds were characterized by spectroscopy and elemental analysis. Many new synthesized compounds showed considerable antimicrobial activity against tested microorganisms. Hydrazones ⁻ and showed remarkable antibacterial and antifungal activities. 4-(2-(-tolyl)hydrazineylidene)-pyrazole-1-carbothiohydrazide displayed the highest antibacterial and antifungal activities with minimum inhibitory concentration (MIC) values lower than standard drugs chloramphenicol and clotrimazole, in the range of 62.5⁻125 and 2.9⁻7.8 µg/mL, respectively.
Topics: Anti-Infective Agents; Bacteria; Chemistry Techniques, Synthetic; Drug Design; Fungi; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles; Thiadiazines
PubMed: 30134530
DOI: 10.3390/molecules23092092 -
Chemistry (Weinheim An Der Bergstrasse,... Oct 2020Convergent routes to a variety of indolines, indoles, oxindoles, and their aza analogues involving radical additions of xanthates are described. Three approaches are... (Review)
Review
Convergent routes to a variety of indolines, indoles, oxindoles, and their aza analogues involving radical additions of xanthates are described. Three approaches are summarized. The first is the least general and relies on the generation of aryl or heteroaryl radicals starting from diazonium salts. The second involves radical addition to N-allylanilines followed by ring-closure onto the aromatic core. A large variety of indolines and azaindolines can thus be obtained and, in many cases, converted into the corresponding indoles and azaindoles by various methods. The synthesis of novel fluoroazaindolines and fluoroazaindoles by a rare homolytic ipso-substitution of fluorine atoms is particularly noteworthy. The last approach hinges on the direct modification of indoles by radical addition to the pyrrole subunit of the indole nucleus. Application of this methodology to the total synthesis of melatonin and the alkaloids mersicarpine, caulerpine, and the pentacyclic skeleton of tronocarpine is briefly discussed. Most of the compounds described herein would be difficult to obtain by more traditional routes.
PubMed: 32314826
DOI: 10.1002/chem.202001341 -
The Journal of Organic Chemistry Feb 2023A simple and concise method for the synthesis of cinnolines has been developed by the reactions of readily available enaminones and aryl diazonium tetrafluoroboronates....
A simple and concise method for the synthesis of cinnolines has been developed by the reactions of readily available enaminones and aryl diazonium tetrafluoroboronates. The reactions run efficiently to provide cinnolines with broad diversity in the substructure by heating in dimethyl sulfoxide without using any catalyst or additive. In addition, the primary investigation of the anti-inflammatory activity of these products leads to the observation of -chlorobenzoyl () and -nitrobenzoyl () cinnolines as attractive anti-inflammatory compounds in vitro.
Topics: Heterocyclic Compounds, 2-Ring; Catalysis; Dimethyl Sulfoxide
PubMed: 36753776
DOI: 10.1021/acs.joc.2c02858 -
Nature Chemical Biology Dec 2021Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health and disease. Due to the non-covalent nature of their interactions and...
Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health and disease. Due to the non-covalent nature of their interactions and their unique partitioning in membranes, the analysis of live-cell, proteome-wide interactions of OHCs remains an unmet challenge. Here, we present a structurally precise chemoproteomics probe for the biologically active molecule 20(S)-hydroxycholesterol (20(S)-OHC) and provide a map of its proteome-wide targets in the membranes of living cells. Our target catalog consolidates diverse OHC ontologies and demonstrates that OHC-interacting proteins cluster with specific processes in immune response and cancer. Competition experiments reveal that 20(S)-OHC is a chemo-, regio- and stereoselective ligand for the protein transmembrane protein 97 (Tmem97/the σ2 receptor), enabling us to reconstruct the 20(S)-OHC-Tmem97 binding site. Our results demonstrate that multiplexed, quantitative analysis of cellular target engagement can expose new dimensions of metabolite activity and identify actionable targets for molecular therapy.
Topics: 3T3 Cells; Animals; Cell Communication; Cell Membrane; Click Chemistry; Diazomethane; HEK293 Cells; Humans; Hydroxycholesterols; Ligands; Mice; Proteome; Pyridinium Compounds; Streptavidin
PubMed: 34799735
DOI: 10.1038/s41589-021-00907-2 -
Bioconjugate Chemistry May 2022Tools to interrogate glycoconjugate-protein interactions in the context of living cells are highly attractive for the identification of critically important functional...
Tools to interrogate glycoconjugate-protein interactions in the context of living cells are highly attractive for the identification of critically important functional binding partners of glycan-binding proteins. These interactions are challenging to study due to the low affinity and rapid dissociation rates of glycan-protein binding events. The use of photo-cross-linkers to capture glycan-protein interaction complexes has shown great promise for identifying binding partners involved in these interactions. Current methodologies use metabolic oligosaccharide engineering (MOE) to incorporate photo-cross-linking sugars. However, these MOE strategies are not amenable to all cell types and can result in low incorporation and cell-surface display of the photo-cross-linking probe, limiting their utility for studying many types of interactions. We describe here an exo-enzymatic strategy for selectively introducing photo-cross-linking probes into cell-surface glycoconjugates using the recombinant human sialyltransferase ST6GAL1 and a diazirine-linked CMP-Neu5Ac derivative. Probe introduction is highly efficient, amenable to different cell types, and resulted in improved cross-linking when compared to MOE. This exo-enzymatic labeling approach can selectively introduce the photo-cross-linking sugar onto specific glycan epitopes and subclasses by harnessing the specificity of the sialyltransferase employed, underscoring its potential as a tool to interrogate and identify glycoconjugate ligands for diverse glycan-binding proteins.
Topics: Cross-Linking Reagents; Diazomethane; Glycoconjugates; Humans; Polysaccharides; Proteins; Sialyltransferases
PubMed: 35426312
DOI: 10.1021/acs.bioconjchem.2c00043 -
Nature Communications Mar 2022π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the...
π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis of complex all-carbon-substituted olefins always draws attention. The difunctionalization of unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues. Here we report the discovery of a regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes. A cationic Pd-catalyzed three-component coupling of aryl diazonium salts, aryl boronic acids (or olefins) and yne-acetates enables access to all-carbon substituted unsymmetrical olefins. The transformation features broad scope with labile functional group tolerance, building broad chemical space of structural diversity (94 molecules). The value of this synthetic method is demonstrated by the direct transformation of natural products and drug candidates containing yne-acetates, to enable highly substituted structurally complex allyl acetate analogues of biologically important compounds. Synthetic versatility of the carboxylate bearing highly substituted olefins is also presented. The reaction outcome is attributed to the in situ formation of stabilized cationic aryl-Pd species, which regulates regioselective aryl-palladation of unsymmetrical yne-acetates. Control experiments reveal the synergy between the carboxylate protecting group and the cationic Pd-intermediate in the regioselectivity and reaction productivity; density functional theory (DFT) studies rationalize the selectivity of the reaction.
Topics: Alkenes; Alkynes; Boronic Acids; Catalysis; Palladium
PubMed: 35296641
DOI: 10.1038/s41467-022-28949-7 -
Chemistry, An Asian Journal Dec 2022An efficient and environmentally-friendly method for carbon-centered radical cyclization of olefins via visible light photoredox catalysis to afford...
An efficient and environmentally-friendly method for carbon-centered radical cyclization of olefins via visible light photoredox catalysis to afford pyrrolo[3,2-c]-quinolines, oxindoles and quinoline-2,4-diones is described. This novel reaction successfully activated the α C-H bonds in one-carbon units such as esters, chlorinated hydrocarbons and cyano compounds via HAT (hydrogen atom transfer) process by means of aryldiazonium salts. The transformation features good functional group tolerance, broad substrate scope, high atom economy, no need for transition metal or high temperature.
Topics: Cyclization; Carbon; Catalysis; Free Radicals; Quinolines; Metals
PubMed: 36332196
DOI: 10.1002/asia.202200963 -
ACS Omega Dec 2019Tyrosine is an attractive target for chemo- and site-selective protein modification. The particular chemical nature of tyrosine residues allows bioconjugation chemistry...
Tyrosine is an attractive target for chemo- and site-selective protein modification. The particular chemical nature of tyrosine residues allows bioconjugation chemistry with reactive aryl diazonium salts via electrophilic aromatic substitution to produce diazo compounds. In this work, we describe the preparation of Cu- and Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-diazonium salts as building blocks for azo coupling chemistry with tyrosine and tyrosine-containing peptides and proteins under mild conditions. 2--(4-aminobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (-NH-Bn-NOTA) was used to form the corresponding Cu- and Ga-labeled complexes, followed by diazotization with NaNO in the presence of HCl. Cu- and Ga-labeled NOTA complexes were prepared in high radiochemical yields >80% starting from 20 μg of -NH-Bn-NOTA. Conversion of -NH-Bn-NOTA complexes into diazonium salts followed by azo coupling with l-tyrosine afforded Cu- and Ga-labeled tyrosine in radiochemical yields of 80 and 56%, respectively. Azo coupling with tyrosine-containing hexapeptide neurotensin NT(8-13) afforded Cu- and Ga-labeled NT(8-13) in radiochemical yields of 45 and 11%, respectively. Azo coupling of Cu-labeled NOTA-diazonium salt with human serum albumin (HSA) gave Cu-labeled HSA in radiochemical yields of 20%. The described azo coupling chemistry represents an innovative and versatile bioconjugation strategy for selective targeting of tyrosine residues in peptides and proteins.
PubMed: 31891090
DOI: 10.1021/acsomega.9b03248 -
Materials (Basel, Switzerland) Feb 2023Water-soluble azo derivatives of lignin were synthesized by the azo coupling reaction using organosolv ethanol lignin and diazonium salts based on sulfanilic acid and...
Water-soluble azo derivatives of lignin were synthesized by the azo coupling reaction using organosolv ethanol lignin and diazonium salts based on sulfanilic acid and p-nitroaniline. The structure of azo derivatives of lignin were studied by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and gel permeation chromatography. It was found that the azobenzene bonds formed in the azo coupling reaction of macromolecules impart the photosensitive properties to the synthesized polymers via cis-trans photoisomerization of the diazobenzene group. It was shown experimentally that the synthesized polymers exhibited good solubility both in the aqueous media in a wide (2-12) pH range and in DMSO and THF organic solvents, which opens up new prospects for their application.
PubMed: 36837154
DOI: 10.3390/ma16041525