546-88-3Relevant articles and documents
Munson,Connors
, p. 1979,1980-1984 (1972)
N-O Bond Fission as the Rate-Determining Step in the Aqueous Conversion of N-Peptidyl-O-(p-nitrobenzoyl)hydroxylamines to p-Nitrobenzoic Acid and Peptidylhydroxamic Acids
Demuth, Hans-Ulrich,Fischer, G.,Barth, A.,Schowen, R. L.
, p. 5880 - 5883 (1989)
N-Acetyl-, N-alanyl-alanyl-, N-alanyl-prolyl-, and N-Boc-alanyl-prolyl-O-(p-nitrobenzoyl) hydroxylamines, compounds that are mechanism-based irreversible inactivators of some proteolytic enzymes, are degraded in aqueous buffers at neutral pH to p-nitrobenzoic acid and either the corresponding N-acylhydroxamic acid or products of its further degradation such as the diketopiperazine.At neutral pH, the reactants exist as the monoanion, as a result of the acidity of the -CO-NH-O- linkage.The p-nitrobenzoic acid formed in a mixture of 50percent H2(18)O and 50percent H2(16)O contains less than 2percent (18)O, which shows that nucleophilic attack of water at the ester carbonyl is not occuring in the degradation.The decomposition of the N-alanyl-prolyl derivative, labeled with (15)N at the N-O nitrogen, exhibits a kinetic isotope effect k14/k15 = 1.092 +/- 0.056, suggesting that N-O fission is occuring in the rate-determining step of the degradation.Kinetic solvent isotope effects of 1.02-1.15 are inconsistent with an expectation of factors around 2 or greater for spontaneous hydrolysis of the ester linkage.All derivatives have ΔH* = 24-27 kcal/mol and ΔS* = +4-7 eu, consistent with unimolecular fission of the substrate N-O to generate p-nitrobenzoate ion and the acyl nitrene.The nitrene must suffer nucleophilic attack at nitrogen very rapidly, producing the hydroxamic acid as the initial product.In the peptide derivatives, further reaction to the cyclized products results.
Activation and Orientation by Receptor-Substrate Binding. The Case of Acyl Transfer from O-Acetylhydroxylamine
Lehn, Jean-Marie,Nishiya, Takako
, p. 215 - 218 (1987)
The strong binding ability of the receptor molecule 1 induces complexation of O-acetylhydroxylamine and of hydroxylamine in their protonated forms; as a result, subsequent reaction of bound CH3COONH3+ becomes fast and selective, giving only acetic acid with a rate enhancement by a factor of about 30.
Bamberger,Seligman
, p. 3885 (1902)
Hydroxamic acids. II. Kinetics and mechanisms of hydroxyaminolysis of succinimide.
Notari
, p. 1064 - 1068 (1969)
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Hydroxamates as a potent skeleton for the development of metallo-β-lactamase inhibitors
Chen, Cheng,Chigan, Jia-Zhu,Ding, Huan-Huan,Li, Jia-Qi,Liu, Lu,Xu, Yin-Sui,Yang, Ke-Wu
, (2021/12/14)
Bacterial resistance caused by metallo-β-lactamases (MβLs) has become an emerging public health threat, and the development of MβLs inhibitor is an effective way to overcome the resistance. In this study, thirteen novel O-aryloxycarbonyl hydroxamates were constructed and assayed against MβLs. The obtained molecules specifically inhibited imipenemase-1 (IMP-1) and New Delhi metallo-β-lactamase-1, exhibiting an IC50 value in the range of 0.10–18.42 and 0.23–22.33?μM, respectively. The hydroxamate 5 was found to be the most potent inhibitor, with an IC50 of 0.1 and 0.23?μM using meropenem and cefazolin as substrates. ICP-MS analysis showed that 5 did not coordinate to the Zn(II) ions at the active site of IMP-1, while the rapid dilution, thermal shift and MALDI-TOF assays revealed that the hydroxamate formed a covalent bond with the enzyme. Cytotoxicity assays indicated that the hydroxamates have low toxicity in MCF-7 cells. This work provided a potent scaffold for the development of MβLs inhibitors.
Alternating Current Electrolysis as Efficient Tool for the Direct Electrochemical Oxidation of Hydroxamic Acids for Acyl Nitroso Diels–Alder Reactions
F?hrmann, Jan,Hilt, Gerhard
supporting information, p. 20313 - 20317 (2021/08/12)
The acyl nitroso Diels–Alder reaction of 1,3-dienes with electrochemically oxidised hydroxamic acids is described. By using alternating current electrolysis, their typical electro-induced decomposition could be suppressed in favour of the 1,2-oxazine cycloaddition products. The reaction was optimised using Design of Experiments (DoE) and a sensitivity test was conducted. A mixture of triethylamine/hexafluoroisopropanol served as supporting electrolyte in dichloromethane, thus giving products of high purity after evaporation of the volatiles without further purification. The optimised reaction conditions were applied to various 1,3-dienes and hydroxamic acids, giving up to 96 % isolated yield.