Redox-Neutral Selenium-Catalysed Isomerisation of para-Hydroxamic Acids into para-Aminophenols.
Ontology highlight
ABSTRACT:
SUBMITTER: Chuang HY
PROVIDER: S-EPMC8252732 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Antioxidant enzyme glutathione peroxidase (GPx) decomposes hydroperoxides by utilizing the different redox chemistry of the selenium and sulfur. Here, we report a Se-catalysed para-amination of phenols while, in contrast, the reactions with sulfur donors are stoichiometric. A catalytic amount of phenylselenyl bromide smoothly converts N-aryloxyacetamides to N-acetyl p-aminophenols. When the para position was substituted (for example, with tyrosine), the dearomatization 4,4-disubstituted cyclodienone products were obtained. A combination of experimental and computational studies was conducted and suggested the weaker Se-N bond plays a key role in the completion of the catalytic cycle. Our method extends the selenium-catalysed processes to the functionalisation of aromatic compounds. Finally, we demonstrated the mild nature of the para-amination reaction by generating an AIEgen 2-(2'-hydroxyphenyl)benzothiazole (HBT) product in a fluorogenic fashion in a PBS buffer.
| S-EPMC6191425 | biostudies-literature
Project description:N-Heterocyclic carbene catalysed redox isomerisation with reduction about the carbonyl has been developed in the transformation of trienyl esters to tetrasubstituted benzaldehydes. The reaction proceeds in good to excellent yield, and in cases that provide 2,2'-biaryls, enantioselectivity is observed. Mechanistic studies demonstrate the intermediacy of a cyclohexenyl β-lactone, while implicating formation of the homoenolate as turnover limiting.
| S-EPMC5645917 | biostudies-literature
Project description:Flavin-dependent 'ene'-reductases (EREDs) are exquisite catalysts for effecting stereoselective reductions. Although these reactions typically proceed through a hydride transfer mechanism, we recently found that EREDs can also catalyse reductive dehalogenations and cyclizations via single electron transfer mechanisms. Here, we demonstrate that these enzymes can catalyse redox-neutral radical cyclizations to produce enantioenriched oxindoles from ?-haloamides. This transformation is a C-C bond-forming reaction currently unknown in nature and one for which there are no catalytic asymmetric examples. Mechanistic studies indicate the reaction proceeds via the flavin semiquinone/quinone redox couple, where ground-state flavin semiquinone provides the electron for substrate reduction and flavin quinone oxidizes the vinylogous ?-amido radical formed after cyclization. This mechanistic manifold was previously unknown for this enzyme family, highlighting the versatility of EREDs in asymmetric synthesis.
| S-EPMC6925616 | biostudies-literature
Project description:AimsVorinostat (suberoylanilide hydroxamic acid; SAHA) is a histone deacetylase inhibitor (HDACi) approved in the clinics for the treatment of T-cell lymphoma and with the potential to be effective also in breast cancer. We investigated the responsiveness to SAHA in human breast primary tumors and cancer cell lines.ResultsWe observed a differential response to drug treatment in both human breast primary tumors and cancer cell lines. Gene expression analysis of the breast cancer cell lines revealed that genes involved in cell adhesion and redox pathways, especially glutathione metabolism, were differentially expressed in the cell lines resistant to SAHA compared with the sensitive ones, indicating their possible association with drug resistance mechanisms. Notably, such an association was also observed in breast primary tumors. Indeed, addition of buthionine sulfoximine (BSO), a compound capable of depleting cellular glutathione, significantly enhanced the cytotoxicity of SAHA in both breast cancer cell lines and primary breast tumors.InnovationWe identify and validate transcriptional differences in genes involved in redox pathways, which include potential predictive markers of sensitivity to SAHA.ConclusionIn breast cancer, it could be relevant to evaluate the expression of antioxidant genes that may favor tumor resistance as a factor to consider for potential clinical application and treatment with epigenetic drugs (HDACis).
| S-EPMC4492673 | biostudies-literature
Project description:Intramolecular carbonyl ene reactions of highly activated enophiles can be catalysed by H-bonding thio-ureas to give tertiary alcohols in high yields without extensive isomerisation side products. An asymmetric variant of this reaction was realised using a chiral thiourea but was limited by low enantioselectivity (up to 33% e.e.) and low turnover frequencies.
| S-EPMC2176055 | biostudies-literature
Project description:Ubiquitous tyrosinase catalyses the aerobic oxidation of phenols to catechols through the binuclear copper centres. Here, inspired by the Fischer indole synthesis, we report an iridium-catalysed tyrosinase-like approach to catechols, employing an oxyacetamide-directed C-H hydroxylation on phenols. This method achieves one-step, redox-neutral synthesis of catechols with diverse substituent groups under mild conditions. Mechanistic studies confirm that the directing group (DG) oxyacetamide acts as the oxygen source. This strategy has been applied to the synthesis of different important catechols with fluorescent property and bioactivity from the corresponding phenols. Finally, our method also provides a convenient route to 18O-labelled catechols using 18O-labelled acetic acid.
| S-EPMC5290158 | biostudies-literature
Project description:A redox-neutral palladium(II)-catalyzed conversion of aryl, heteroaryl, and alkenyl boronic acids into sulfinate intermediates, and onwards to sulfones and sulfonamides, has been realized. A simple Pd(OAc)2 catalyst, in combination with the sulfur dioxide surrogate 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO), is sufficient to achieve rapid and high-yielding conversion of the boronic acids into the corresponding sulfinates. Addition of C- or N-based electrophiles then allows conversion into sulfones and sulfonamides, respectively, in a one-pot, two-step process.
| S-EPMC4832823 | biostudies-literature
Project description:The direct α-arylation/N-alkylation of cyclic amines was achieved in a redox-neutral fashion under mild conditions. Transformations occur in the absence of any additives or are promoted by simple carboxylic acids.
| S-EPMC3946350 | biostudies-literature
Project description:The facile rearrangement of "S-acyl isopeptides" to native peptide bonds via S,N-acyl shift is central to the success of native chemical ligation, the widely used approach for protein total synthesis. Proximity-driven amide bond formation via acyl transfer reactions in other contexts has proven generally less effective. Here, we show that under neutral aqueous conditions, "O-acyl isopeptides" derived from hydroxy-asparagine [aspartic acid-?-hydroxamic acid; Asp(?-HA)] rearrange to form native peptide bonds via an O,N-acyl shift. This process constitutes a rare example of an O,N-acyl shift that proceeds rapidly across a medium-size ring (t1/2 ? 15 min), and takes place in water with minimal interference from hydrolysis. In contrast to serine/threonine or tyrosine, which form O-acyl isopeptides only by the use of highly activated acyl donors and appropriate protecting groups in organic solvent, Asp(?-HA) is sufficiently reactive to form O-acyl isopeptides by treatment with an unprotected peptide-?thioester, at low mM concentration, in water. These findings were applied to an acyl transfer-based chemical ligation strategy, in which an unprotected N-terminal Asp(?-HA)-peptide and peptide-?thioester react under aqueous conditions to give a ligation product ultimately linked by a native peptide bond.
| S-EPMC5899448 | biostudies-other
Project description:Histone deacetylases (HDACs) play an essential role in the transcriptional regulation of cells through the deacetylation of nuclear histone and non-histone proteins and are promising therapeutic targets for the treatment of various diseases. Here, the synthesis of new compounds in which a hydroxamic acid residue is attached to differently substituted pyrimidine rings via a methylene group bridge of varying length as potential HDAC inhibitors is described. The target compounds were obtained by alkylation of 2-(alkylthio)pyrimidin-4(3H)-ones with ethyl 2-bromoethanoate, ethyl 4-bromobutanoate, or methyl 6-bromohexanoate followed by aminolysis of the obtained esters with hydroxylamine. Oxidation of the 2-methylthio group to the methylsulfonyl group and following treatment with amines resulted in the formation of the corresponding 2-amino-substituted derivatives, the ester group of which reacted with hydroxylamine to give the corresponding hydroxamic acids. The synthesized hydroxamic acids were tested as inhibitors of the HDAC4 and HDAC8 isoforms. Among the synthesized pyrimidine-based hydroxamic acids N-hydroxy-6-[6-methyl-2-(methylthio)-5-propylpyrimidin-4-yloxy]hexanamide was found to be the most potent inhibitor of both the HDAC4 and HDAC8 isoforms, with an IC50 of 16.6 µM and 1.2 µM, respectively.
| S-EPMC9296983 | biostudies-literature