3382-63-6Relevant articles and documents
A New Pathway for Protein Haptenation by β-Lactams
Pérez-Ruíz, Raúl,Lence, Emilio,Andreu, Inmaculada,Limones-Herrero, Daniel,González-Bello, Concepción,Miranda, Miguel A.,Jiménez, M. Consuelo
, p. 13986 - 13994 (2017)
The covalent binding of β-lactams to proteins upon photochemical activation has been demonstrated by using an integrated approach that combines photochemical, proteomic and computational studies, selecting human serum albumin (HSA) as a target protein and ezetimibe (1) as a probe. The results have revealed a novel protein haptenation pathway for this family of drugs that is an alternative to the known nucleophilic ring opening of β-lactams by the free amino group of lysine residues. Thus, photochemical ring splitting of the β-lactam ring, following a formal retro-Staudinger reaction, gives a highly reactive ketene intermediate that is trapped by the neighbouring lysine residues, leading to an amide adduct. For the investigated 1/HSA system, covalent modification of residues Lys414 and Lys525, which are located in sub-domains IIIA and IIIB, respectively, occurs. The observed photobinding may constitute the key step in the sequence of events leading to photoallergy. Docking and molecular dynamics simulation studies provide an insight into the molecular basis of the selectivity of 1 for these HSA sub-domains and the covalent modification mechanism. Computational studies also reveal positive cooperative binding of sub-domain IIIB that explains the experimentally observed modification of Lys414, which is located in a barely accessible pocket (sub-domain IIIA).
Additional effect of para-hydroxyl on the reduction potentials of the N-benzylidenebenzenamines
Cao, Chao-Tun,Zhou, Wei,Cao, Chenzhong
, (2019/12/27)
The reduction potential ERed of disubstituted N-benzylidenebenzenamines XArCH NArY (abbreviated as XBAY) is a measure of the electron acceptance ability of the Lowest-energy Unoccupied Molecular Orbital (LUMO) in molecule, which is closely related to the electronic effects of substituents X and Y in molecule. Previous studies on the ERed of XBAY reported by Luo, Wang, and Yuan all did not involve these molecules containing hydroxyl. In this work, 28 samples of disubstituted N-benzylidenebenzenamines containing para-hydroxyl, (abbreviated as 4-OHBAY or XBAOH-4′) were synthesized, and their ERed values were measured. Then, 127 compounds were taken as a complicated ERed data set, which involved 28 compounds (4-OHBAY and XBAOH-4′) of this work and 99 compounds XBAY reported by Luo. Based on these data ERed set, through a quantitative regression analysis method and comparison of the factors affecting the ERed, the following results are obtained: (a) Because the phenolic hydroxyl OH can dissociate H+ to form phenolic oxygen anion, the change regularity of ERed of compounds 4-OHBAY and XBAOH-4′ is somewhat different from that of ERed of XBAY compounds without hydroxyl OH. That is, hydroxyl OH has an additional effect on the ERed, which decreases the ERed value. (b) The additional effects of 4-OH on the ERed is different from that of 4′-OH. The effect of hydroxyl OH attached to the aldehyde aromatic ring on the ERed is more than that of OH attached to the amine aromatic ring.
Iron-Catalyzed Nitrene Transfer Reaction of 4-Hydroxystilbenes with Aryl Azides: Synthesis of Imines via C=C Bond Cleavage
Peng, Yi,Fan, Yan-Hui,Li, Si-Yuan,Li, Bin,Xue, Jing,Deng, Qing-Hai
, p. 8389 - 8394 (2019/10/16)
C=C bond breaking to access the C=N bond remains an underdeveloped area. A new protocol for C=C bond cleavage of alkenes under nonoxidative conditions to produce imines via an iron-catalyzed nitrene transfer reaction of 4-hydroxystilbenes with aryl azides is reported. The success of various sequential one-pot reactions reveals that the good compatibility of this method makes it very attractive for synthetic applications. On the basis of experimental observations, a plausible reaction mechanism is also proposed.
METHOD FOR PREPARING AZETIDINONE COMPOUND AND INTERMEDIATE OF AZETIDINONE COMPOUND
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Paragraph 0054-0056, (2017/05/31)
Disclosed is a new method for preparing an azetidinone compound represented by formula (I). The carboxylic ketoester represented by formula (II) serves as the raw material and is subjected to Grignard addition, stereoselective dehydration, ester group reduction, hydroxyl group protection, addition with imine after condensation with a chiral auxiliary, cyclization and deprotection to obtain the compound represented by formula (I). The present invention has advantages of easily available raw material, a few synthetic steps, simple operation, high yield, good stereoselectivity and low cost, and can be used for industrial production.
