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.
Characterization and cytotoxicity evaluation of biocompatible amino acid esters used to convert salicylic acid into ionic liquids
Moshikur, Rahman Md.,Chowdhury, Md. Raihan,Wakabayashi, Rie,Tahara, Yoshiro,Moniruzzaman, Muhammad,Goto, Masahiro
, p. 31 - 38 (2018/05/28)
The technological utility of active pharmaceutical ingredients (APIs) is greatly enhanced when they are transformed into ionic liquids (ILs). API-ILs have better solubility, thermal stability, and the efficacy in topical delivery than solid or crystalline drugs. However, toxicological issue of API-ILs is the main challenge for their application in drug delivery. To address this issue, 11 amino acid esters (AAEs) were synthesized and investigated as biocompatible counter cations for the poorly water-soluble drug salicylic acid (Sal) to form Sal-ILs. The AAEs were characterized using 1H and 13C NMR, FTIR, elemental, and thermogravimetric analyses. The cytotoxicities of the AAE cations, Sal-ILs, and free Sal were investigated using mammalian cell lines (L929 and HeLa). The toxicities of the AAE cations greatly increased with inclusion of long alkyl chains, sulfur, and aromatic rings in the side groups of the cations. Ethyl esters of alanine, aspartic acid, and proline were selected as a low cytotoxic AAE. The cytotoxicities of the Sal-ILs drastically increased compared with the AAEs on incorporation of Sal into the cations, and were comparable to that of free Sal. Interestingly, the water miscibilities of the Sal-ILs were higher than that of free Sal, and the Sal-ILs were miscible with water at any ratio. A skin permeation study showed that the Sal-ILs penetrated through skin faster than the Sal sodium salt. These results suggest that AAEs could be used in biomedical applications to eliminate the use of traditional toxic solvents for transdermal delivery of poorly water-soluble drugs.
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).
Butyryl glutamic acid derivative as well as composition and application thereof
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Paragraph 0116; 0117, (2018/07/30)
The invention discloses a butyryl glutamic acid derivative as well as a composition and application thereof. The butyryl glutamic acid derivative disclosed by the invention or a racemic modification,stereisomer, geometric isomer, tautomer and solvate or feed-acceptable salt thereof can be applied in the preparation of novel feed additives and feeds. The invention further discloses a feed composition of the butyryl glutamic acid derivative or the racemic modification, the stereisomer, the geometric isomer, the tautomer and the solvate or the feed-acceptable salt thereof. When applied in animalhusbandry, the butyryl glutamic acid derivative provided by the invention has the effect of improving the production performance of animals, such as increasing animal weight increasing rate, decreasing feed conversion ratio and controlling diarrhea rate, and can be applied as an effective, safe novel feed additive.
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.
Chiral 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimine analogues as novel potent neonicotinoids: Synthesis, insecticidal evaluation and molecular docking studies
Sun, Chuanwen,Zhu, Jun,Wang, Haifeng,Jin, Jia,Xing, Jiahua,Yang, Dingrong
experimental part, p. 11 - 20 (2011/02/27)
A new series of 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimines (4a-4x) were designed and synthesized as novel chiral neonicotinoid analogues. The single-crystal structure of 4n was further determined by X-ray diffraction, and its S configuration was confirmed. Preliminary bioassay showed that compound 4e, 4k, 4u, 4v exhibited excellent insecticidal activities at 100 mg/L, while 4k had >90% mortality at 10 mg/L, which suggested it could be used as a lead for future development. Modeling the inhibitor-nAChR complexes by molecular docking studies explained the structure-activity relationships observed in vitro, and revealed an intriguing molecular binding mode at the active site of nAChR, which raised the possibility that these analogues may arbitrate their insecticidal activity through a mechanism other than imidacloprid.
Use of diphenyliodonium bromide in the synthesis of some N-phenyl-amino acids
McKerrow, Jason D.,Al-Rawi, Jasim M. A.,Brooks, Peter
experimental part, p. 1161 - 1179 (2010/04/28)
The N-phenyl methyl esters 4 of glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, serine, threonine, tyrosine, aspartic acid, and glutamic acid have been synthesized in good to excellent yields using diphenyliodonium bromide, AgNO3, and a catalytic amount of CuBr starting from the relevant amino acid ester. The chiral integrity of the amino acids 5 was maintained during these reactions, which were confirmed by the synthesis of dipeptide for each N-phenyl amino acid. The structures of the new compounds were confirmed by the analysis of their IR, 1H, and 13C NMR spectra in addition to CHN microanalysis or high-resolution mass spectrometry for the new N-phenyl amino acids 5 and the esters 4.
Antiviral phosphoramidates
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Page/Page column 18, (2008/06/13)
The invention provides novel nucleoside compounds of formula I wherein R1, R2a, R2b, R3, R4, R5, R6, R8a, R9 and R10 are as defined herein which are useful for the treatment of Hepatitis C Virus (HCV) mediated diseases. The invention further provides methods for treatment or prophylaxis of HCV mediated diseases with compounds of formula I and pharmaceutical compositions comprising these compounds,
TRANSFORMATION OF GLYCYRRHIZIC ACID. VII. SYNTHESIS OF TRITERPENE GLYCOPEPTIDES CONTAINING ALKYL ESTERS OF L-AMINO ACIDS
Baltina, L.A.,Ryzhova, S.A.,Vasil'eva, E.V.,Tolstikov, G.A.
, p. 238 - 244 (2007/10/02)
The synthesis has been effected by the activated N-hydroxy succinimide ester method of new triterpene glycopeptides derived from glycyrrhizic acid, containing fragments of alkyl (ethyl, propyl, butyl) esters of L-amino acids.
PREPARATION OF OPTICALLY PURE ω-HYDROXYMETHYL LACTAMS
Huang, Sung-Ben,Nelson, Jeffrey S.,Weller, Dwight D.
, p. 3485 - 3496 (2007/10/02)
Thermal cyclization of L-glutamate and L-α-aminoadipate to the corresponding lactam esters can be achieved without racemization.LiBH4 reduction of the esters provides optically pure hydroxymethyl lactams.
