1118-89-4Relevant articles and documents
Simple and convenient preparation method of relebactam
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Paragraph 0089-0090, (2020/05/09)
The invention discloses a simple and convenient preparation method of relebactam. According to the method, a key intermediate (2S,5R)-5-benzyloxyamino piperidine-2-formic acid is prepared by using (S)-N-protective group-5-oxo-2-piperidinecarboxylic acid or a salt form thereof as an initial raw material; the (2S,5R)-5-benzyloxyamino piperidine-2-formic acid and phosgene, solid phosgene or diphosgene are subjected to acylating chlorination, cyclic ureation, and reaction with 1-protective group-4-aminopiperidine to obtain (2S,5R)-6-benzyloxy-N-(1-protective group-4-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide; and debenzylation, sulfonyl oxidation, ammonium salt formation and deprotection are performed to prepare relebactam. According to the invention, the raw materials are cheap, easyto obtain and low in cost, the technological process is safe, simple and convenient to operate, small in wastewater and waste salt yield and environmentally friendly, the reaction atom economy is high, the reaction selectivity of each step is high, the purity and the yield are high, and industrial production is facilitated.
Green preparation method of N-substituted-L-pyroglutamate
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Paragraph 0051; 0052, (2018/03/28)
The invention provides a green preparation method of N-substituted-L-pyroglutamate. The method comprises the steps as follows: L-glutamic acid diester hydrochloride (III) is prepared from L-glutamic acid (II) as a starting material in the presence of an acidic reagent by an esterification reaction; then, L-glutamic acid diester hydrochloride (III) is subjected to N-substituted protective reactionwith an N-substituent protective reagent with a one-pot method in the presence of a base and a solvent, an N-substituted protective group is introduced, heating is performed for dealcoholization cyclization in molecules, and N-substituted-L-pyroglutamate as shown in the formula (I) is obtained. The method has the advantages of cheap and easily available raw materials, classic reaction types, shortprocess route, simple and convenient operation, small waste water amount, green and environment-friendly production process, high reaction yield and low product cost. 5R-benzyloxyaminopiperidine-2S-carboxylate, 5R-benzyloxyaminopiperidine-2S-formate ethanedioate and avibactam can be prepared from N-substituted-L-pyroglutamate as shown in the formula (I).
Glutathione peroxidase-like activity of amino-substitutedwater-soluble cyclic selenides: A shift of the major catalytic cycle in methanol
Arai, Kenta,Tashiro, Ayako,Osaka, Yuui,Iwaoka, Michio
supporting information, (2017/03/09)
We previously reported that water-soluble cyclic selenides can mimic the antioxidative function of glutathione peroxidase (GPx) in water through a simple catalytic cycle, in which the selenide (>Se) is oxidized by H2O2 to the selenoxide (>Se=O) and the selenoxide is reduced by a thiol back to the selenide. In methanol, however, the GPx-like activity could not be explained by this simple scenario. To look into the reasons for the unusual behaviors in methanol, monoamino-substituted cyclic selenides with a variable ring size were synthesized, and the intermediates of the catalytic cycle were characterized by means of 77Se-NMR and LC-MS spectroscopies. In water, it was confirmed that the selenide and the selenoxide mainly contribute to the antioxidative function, though a slight contribution from the dihydroxy selenane (>Se(OH)2) was also suggested. In methanol, on the other hand, other active species, such as hydroxyselenonium (>Se+-OH) and hydroxy perhydroxy selenane (>Se(OH)(OOH)), could be generated to build another catalytic cycle. This over-oxidation would be more feasible for amino-substituted cyclic selenides, probably because the ammonium (NH3 +) group would transfer a proton to the selenoxide moiety to produce a hydroxyselenonium species in the absence of an additional proton source. Thus, a shift of the major catalytic cycle in methanol would make the GPx-like antioxidative function of selenides perplexing.