- Azetidinimines as a novel series of non-covalent broad-spectrum inhibitors of β-lactamases with submicromolar activities against carbapenemases KPC-2 (class A), NDM-1 (class B) and OXA-48 (class D)
-
The occurrence of resistances in Gram negative bacteria is steadily increasing to reach extremely worrying levels and one of the main causes of resistance is the massive spread of very efficient β-lactamases which render most β-lactam antibiotics useless. Herein, we report the development of a series of imino-analogues of β-lactams (namely azetidinimines) as efficient non-covalent inhibitors of β-lactamases. Despite the structural and mechanistic differences between serine-β-lactamases KPC-2 and OXA-48 and metallo-β-lactamase NDM-1, all three enzymes can be inhibited at a submicromolar level by compound 7dfm, which can also repotentiate imipenem against a resistant strain of Escherichia coli expressing NDM-1. We show that 7dfm can efficiently inhibit not only the three main clinically-relevant carbapenemases of Ambler classes A (KPC-2), B (NDM-1) and D (OXA-48) with Ki's below 0.3 μM, but also the cephalosporinase CMY-2 (class C, 86% inhibition at 10 μM). Our results pave the way for the development of a new structurally original family of non-covalent broad-spectrum inhibitors of β-lactamases.
- Romero, Eugénie,Oueslati, Saoussen,Benchekroun, Mohamed,D'Hollander, Agathe C.A.,Ventre, Sandrine,Vijayakumar, Kamsana,Minard, Corinne,Exilie, Cynthia,Tlili, Linda,Retailleau, Pascal,Zavala, Agustin,Elisée, Eddy,Selwa, Edithe,Nguyen, Laetitia A.,Pruvost, Alain,Naas, Thierry,Iorga, Bogdan I.,Dodd, Robert H.,Cariou, Kevin
-
supporting information
(2021/04/19)
-
- Fluorodynamers Displaying Tunable Fluorescence on Constitutional Exchanges in Solution and at Solid Film–Solution Interface
-
Dynamic covalent polymers—dynamers—are adaptive materials that offer timely variant adaptive macroscopic organization across extended scales. In the current study, imine exchange reactions and fluorescence transfer can occur at the interfaces between vari
- Si, Mingran,Zhu, Weijia,Zhang, Yan,Barboiu, Mihail,Chen, Jinghua
-
supporting information
p. 10191 - 10194
(2020/07/13)
-
- Enantioselective Direct anti-Selective Mannich-type Reactions Catalyzed by 3-Pyrrolidinecarboxylic Acid in the Presence of Potassium Carbonate: Addition of Potassium Carbonate Improves Enantioselectivities
-
Mannich-type reactions of cyclohexanone and related six-membered-ring ketones with N-p-methoxyphenyl-protected imines of arylaldehydes catalyzed by 3-pyrrolidinecarboxylic acid in the presence of K2CO3 that afford anti-isomers of the Mannich products with
- Garg, Yuvraj,Tanaka, Fujie
-
supporting information
p. 4542 - 4546
(2020/06/08)
-
- Visible-Light-Mediated, Chemo- and Stereoselective Radical Process for the Synthesis of C-Glycoamino Acids
-
An approach for efficient synthesis of C-glycosyl amino acids is described. Different from typical photoredox-catalyzed reactions of imines, the new process follows a pathway in which α-imino esters serve as electrophiles in chemoselective addition reactions with nucleophilic glycosyl radicals. The process is highlighted by the mild nature of the reaction conditions, the highly stereoselectivity attending C-C bond formation, and its applicability to C-glycosylations using both armed and disarmed pentose and hexose derivatives.
- Ji, Peng,Zhang, Yueteng,Wei, Yongyi,Huang, He,Hu, Wenbo,Mariano, Patrick A.,Wang, Wei
-
supporting information
p. 3086 - 3092
(2019/05/01)
-
- One-pot sequential multicomponent reaction between: In situ generated aldimines and succinaldehyde: Facile synthesis of substituted pyrrole-3-carbaldehydes and applications towards medicinally important fused heterocycles
-
An efficient sequential multi-component method for the synthesis of N-Arylpyrrole-3-carbaldehydes has been developed. This reaction involved a proline-catalyzed direct Mannich reaction-cyclization sequence between succinaldehyde and in situ generated Ar/H
- Singh, Anoop,Mir, Nisar A.,Choudhary, Sachin,Singh, Deepika,Sharma, Preetika,Kant, Rajni,Kumar, Indresh
-
p. 15448 - 15458
(2018/05/03)
-
- Paclitaxel Biosynthesis: Adenylation and Thiolation Domains of an NRPS TycA PheAT Module Produce Various Arylisoserine CoA Thioesters
-
Structure-activity relationship studies show that the phenylisoserinyl moiety of paclitaxel (Taxol) is largely necessary for the effective anticancer activity. Several paclitaxel analogues with a variant isoserinyl side chain have improved pharmaceutical
- Muchiri, Ruth,Walker, Kevin D.
-
p. 1415 - 1425
(2017/03/23)
-
- Properties of liquid crystals and Cu2+ recognition based on Schiff bases
-
Two series of new Schiff base compounds were synthesized. For Schiff base compounds with a pyridine nitrogen atom in 4-position (7a-e), their supramolecular hydrogen bonding complexes show good liquid crystal properties. However, no liquid crystal property is observed for 8a-e. Results of theoretical calculations demonstrate that it is the intermolecular hydrogen bond of Schiff base compounds (8a-e) that prevents the formation of supramolecular hydrogen bonding. The Schiff base compounds, with terminal alkoxy chains, can recognize Cu2+ selectively with a color change. Nevertheless, others cannot recognize Cu2+.
- Liu, Zhilian,Yu, Zhenning,Zhang, Jian,Zhang, Shuxiang
-
-
- Enantioselective synthesis of 1,2,5,6-tetrahydropyridines (THPs): Via proline-catalyzed direct Mannich-cyclization/domino oxidation-reduction sequence: Application for medicinally important N-heterocycles
-
An enantioselective multi-component synthesis of 1,2,5,6-tetrahydropyridines (THPs) has been developed through a one-pot domino-process. This transformation proceeds through proline-catalyzed direct Mannich reaction-cyclization of glutaraldehyde with in s
- Ramaraju, Panduga,Mir, Nisar A.,Singh, Deepika,Kumar, Indresh
-
p. 60422 - 60432
(2016/07/11)
-
- Catalytic asymmetric synthesis of dihydroquinazolinones from imines and 2-aminobenzamides
-
An unprecedented catalytic asymmetric synthesis of aminal-containing heterocyclic compounds has been developed from imines and tethered nitrogen/nitrogen nucleophiles. In the presence of 10mol% of a commercially available chiral phosphoric acid, a range of aromatic, α,β- unsaturated, and aliphatic imines react with 2-aminobenzamides to give dihydroquinazolinones in good to excellent yields and ee. The enantioselectivity is significantly affected by the imine N-substituent through non-bonding interactions with the chiral phosphoric acid and the 2-aminobenzamide. Copyright
- Cheng, Dao-Juan,Tian, Yu,Tian, Shi-Kai
-
supporting information; experimental part
p. 995 - 999
(2012/06/01)
-
- An efficient and convenient synthesis of ethyl 1-(4-Methoxyphenyl)-5- phenyl-1H-1,2,3-triazole-4-carboxylate
-
The "click chemistry" of using organic azides and terminal alkynes is arguably the most efficient and straightforward route to the synthesis of 1,2,3-triazoles. In this paper, an alternative and direct access to ethyl 1-(4-methoxyphenyl)-5-phenyl-1H-1,2,3
- Chen, Jung-Hsuan,Liu, Shuan-Ru,Chen, Kwunmin
-
experimental part
p. 328 - 333
(2010/07/05)
-
- Palladium-catalyzed allylation of imines with allyl alcohols
-
(Chemical Equation Presented) A catalytic system, Pd(OAc)2 (10 mol %)-P(n-Bu)3 (20 mol %)-Et3B (360 mol %), promotes allylic alcohols to undergo the allylation of anisidineimines of aromatic and aliphatic aldehydes and furnishes homoallylamines in good to moderate yields. The reaction shows unique stereoselectivity, giving anti-isomers selectively.
- Shimizu, Masamichi,Kimura, Masanari,Watanabe, Toshiya,Tamaru, Yoshinao
-
p. 637 - 640
(2007/10/03)
-