166330-03-6Relevant articles and documents
Neighboring phenolic group-activated: Gem -difluoroallylboration of imines for the catalyst-free synthesis of gem -difluorohomoallylamines
Yang, Xing,Zhang, Feng,Zhou, Yang,Huang, Yi-Yong
, p. 3367 - 3371 (2018)
We herein report an unprecedented addition reaction of pinacol gem-difluoroallylborates and imines enabled by a neighboring phenolic group in an N-protecting group under catalyst-free conditions, thus facilitating the construction of a wide range of racemic gem-difluorohomoallylamine derivatives. Based on the control experiments, a plausible transition state via the Zimmerman-Traxler model was proposed to elucidate the significance of the neighboring phenolic group, as well as the γ-selectivity of the boronate reagents.
Mercapto-amide boronic acid derivative and application thereof as MBL (metal beta-lactamase) and/or SBL (serine beta-lactamase) inhibitor
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Paragraph 0062-0065, (2019/09/14)
The invention provides a compound of a formula (I) shown in the specification, or a conformational isomer, or an optical isomer or a pharmaceutically acceptable salt thereof. The compound of the formula (I) shown in the specification has excellent broad-spectrum inhibitory activity on MBL (metal beta-lactamase) and/or SBL (serine beta-lactamase), and can be used for preparing MBL and/or SBL inhibitors. Moreover, the compound disclosed by the invention has excellent antibacterial activity on multiple drug-resistant bacteria and is capable of reversing drug resistance of carbapenem drug-resistant bacteria, and the antibacterial effect of the compound is prior to those of positive control products such as L-captopril and tazobactam. The compound disclosed by the invention has very great potential in preparation of MBL/SBL dual inhibitors and medicines reversing drug resistance of carbapenem drug-resistance bacteria.
Structure-based development of (1-(3′-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- And Serine-β-lactamases
Wang, Yao-Ling,Liu, Sha,Yu, Zhu-Jun,Lei, Yuan,Huang, Meng-Yi,Yan, Yu-Hang,Ma, Qiang,Zheng, Yang,Deng, Hui,Sun, Ying,Wu, Chengyong,Yu, Yamei,Chen, Qiang,Wang, Zhenling,Wu, Yong,Li, Guo-Bo
, p. 7160 - 7184 (2019/08/28)
The emergence and spread of bacterial pathogens acquired metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) medicated β-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2′S)-(1-(3′-mercapto-2′-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.
A Modular Approach to the Asymmetric Synthesis of Cytisine
Struth, Felix R.,Hirschhaüser, Christoph
supporting information, p. 958 - 964 (2016/03/01)
The asymmetric synthesis of (+)-and (-)-cytisine starts with Matteson homologations for the construction of a chiral C3-building block. Conversion of the C3-building block into a dihydropyridone is achieved by straightforward functional group interconversions and ring closing metathesis. After bromination, this central building block was diastereospecifically converted into cytisine in five steps.
Br?nsted Acid Catalyzed gem-Difluoroallylation of Aldehydes and Ketone with β-Tosyloxy-γ,γ-difluroallylboronic Acid Pinacol Ester
Zhang, Bo,Zhang, Xingang
supporting information, p. 477 - 480 (2016/05/24)
A shelf-stable gem-difluorinated reagent β-tosyloxy-γ,γ-difluroallylboronic acid pinacol ester has been prepared, which can be easily used for the preparation of gem-difluorinated homoallylic alcohols through Br?nsted acid (PhCO2H) catalyzed ge
NOVEL DIAMINE COMPOUND AND METAL COMPLEXES, AND METHOD FOR PRODUCING OPTICALLY ACTIVE COMPOUNDS
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Paragraph 0160; 0161, (2015/04/15)
The present invention relates to a novel diamine compound represented by the general formula (1), a ruthenium-diamine complex, an iridium-diamine complex, and a rhodium-diamine complex having the diamine compound as a ligand. Furthermore, the present inve
Facile synthesis of borofragments and their evaluation in activity-based protein profiling
Adachi, Shinya,Cognetta, Armand B.,Niphakis, Micah J.,He, Zhi,Zajdlik, Adam,St. Denis, Jeffrey D.,Scully, Conor C. G.,Cravatt, Benjamin F.,Yudin, Andrei K.
supporting information, p. 3608 - 3611 (2015/04/21)
The discovery of enzyme inhibitors relies on synthetic methods that enable rapid and modular construction of small molecules. Heterocyclic fragments designed to maximize enthalpic interactions with their protein targets represent a particularly desirable class of molecules. Here we describe a reagent that enables straightforward construction of borofragments , in which a heterocycle is separated from the boron center by two or three rotatable bonds. The stability of these molecules depends on the MIDA group which likely acts as a slow-release element under biological conditions. Borofragments can be used to discover inhibitors of enzymes that use catalytic oxygen nucleophiles. We have employed this method to identify inhibitors of ABHD10 and the predicted carboxypeptidase CPVL. This technique should be applicable to other classes of targets. This journal is
Stereocontrolled synthesis of adjacent acyclic quaternary-tertiary motifs: Application to a concise total synthesis of (-)-filiformin
Blair, Daniel J.,Fletcher, Catherine J.,Wheelhouse, Katherine M. P.,Aggarwal, Varinder K.
supporting information, p. 5552 - 5555 (2014/06/10)
Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary-tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel-type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps have been applied to the shortest enantioselective synthesis of (-)-filiformin to date (9 steps) with full stereocontrol. True to (fili)form: Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary-tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel-type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps were applied to the enantioselective synthesis of (-)-filiformin.
Nucleophilic fluoroalkylation of (bromomethyl)pinacolborane using silicon reagents
Levin, Vitalij V.,Elkin, Pavel K.,Struchkova, Marina I.,Dilman, Alexander D.
, p. 43 - 46 (2013/11/06)
A method for the synthesis of pinacol boronic esters bearing a fluorinated group at the a-carbon atom (RfCH2Bpin) from corresponding bromomethyl borane (BrCH2Bpin) and fluorinated silanes (RfSiMe3) is described. The fluoroalkylation reaction involves formation of borate anions followed by intramolecular nucleophilic substitution of bromine.
