45709-05-5Relevant articles and documents
Discovery of pyrrolidine-2,3-diones as novel inhibitors of p. Aeruginosa pbp3
López-Pérez, Arancha,Freischem, Stefan,Grimm, Immanuel,Weiergr?ber, Oliver,Dingley, Andrew J.,López-Alberca, María Pascual,Waldmann, Herbert,Vollmer, Waldemar,Kumar, Kamal,Vuong, Cuong
, (2021/05/21)
The alarming threat of the spread of multidrug resistant bacteria currently leaves clinicians with very limited options to combat infections, especially those from Gram-negative bacteria. Hence, innovative strategies to deliver the next generation of antibacterials are urgently needed. Penicillin binding proteins (PBPs) are proven targets inhibited by β-lactam antibiotics. To discover novel, non-β-lactam inhibitors against PBP3 of Pseudomonas aeruginosa, we optimised a fluorescence assay based on a well-known thioester artificial substrate and performed a target screening using a focused protease-targeted library of 2455 compounds, which led to the identification of pyrrolidine-2,3-dione as a potential scaffold to inhibit the PBP3 target. Further chemical optimisation using a one-pot three-component reaction protocol delivered compounds with excellent target inhibition, initial antibacterial activities against P. aeruginosa and no apparent cytotoxicity. Our investigation revealed the key structural features; for instance, 3-hydroxyl group (R2) and a heteroaryl group (R1) appended to the N-pyrroldine-2,3-dione via methylene linker required for target inhibition. Overall, the discovery of the pyrrolidine-2,3-dione class of inhibitors of PBP3 brings opportunities to target multidrug-resistant bacterial strains and calls for further optimisation to improve antibacterial activity against P. aeruginosa.
One-pot multicomponent reaction of catechols, ammonium acetate, and aldehydes for the synthesis of benzoxazole derivatives using the fe(iii)-salen complex
Sharghi, Hashem,Aboonajmi, Jasem,Aberi, Mahdi
, p. 6567 - 6577 (2020/06/08)
The Fe(III)-salen complex has been applied successfully as a catalyst for the novel, simple, efficient, and one-pot multicomponent synthesis of benzoxazole derivatives from catechols, ammonium acetate as the nitrogen source, and aldehydes (nontoxic and cheap alternatives of amines) for the first time. Using this procedure, a wide range of benzoxazoles was successfully synthesized in the presence of a catalyst in EtOH under mild conditions, and all products were obtained in excellent yields. To the best of our knowledge, this method is the first example of the multicomponent synthesis of benzoxazole derivatives using these starting materials. The notable features such as the use of air that is considered as a benign oxidant and EtOH as a green solvent, ease of product separation, readily available and inexpensive aldehydes, and mild conditions make our procedure more efficient and practical for organic synthesis. Moreover, the current protocol is successfully applied to synthesize desirable products on a large scale.
Kinetic Resolution of Secondary Allyl Boronates and Their Application in the Synthesis of Homoallylic Amines
Villar, Laura,Orlov, Nikolai V.,Kondratyev, Nikolay S.,Uria, Uxue,Vicario, Jose L.,Malkov, Andrei V.
supporting information, p. 16262 - 16265 (2018/10/20)
Highly enantioenriched, chromatographically-stable secondary allyl boronates featuring a 1,1,2,2-tetraethyl-1,2-ethanediol fragment (Epin) were obtained by kinetic resolution of their racemic mixtures. The Epin group at boron considerably improved stability of allyl boronates allowing them to be readily isolated by chromatography on silica. The resolved reagents were applied in stereoselective synthesis of homoallylic amines with an internal double bond employing unprotected imines formed in situ from aldehydes and ammonia. The reactions proceeded with an excellent transfer of chirality.
