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.
Synthetic method for acetylhydroxylamine
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Paragraph 0026-0029, (2021/08/06)
The invention provides a synthesis method for acetylhydroxylamine. The method adopts a two-step method to synthesize acetylhydroxylamine, a first micro-channel reactor and a second micro-channel reactor are used for replacing a traditional reaction bottle. The complete dissolution concentration of hydroxylamine hydrochloride in water is 42%, and 30% sodium hydroxide solution is prepared. The hydroxylamine hydrochloride aqueous solution and the sodium hydroxide aqueous solution are simultaneously fed into a first micro-channel reactor by using different metering pumps to react, the reaction temperature is controlled to be 20-25 DEG C, reaction liquid is collected, the obtained reaction liquid and ethyl acetate are simultaneously fed into a second micro-channel reactor to react, the reaction temperature is controlled to be 30-35 DEG C, and after the reaction is finished, distilling is conducted to obtain acetylhydroxylamine. The synthetic method of acetylhydroxylamine is improved, the raw materials are simple, the reaction is easy to control, the process is simple, waste is few, the total yield can reach 98%, and the synthetic method is suitable for industrial production.