The effectiveness of β-lactam antibiotics is increasingly compromised by β-lactamases. Boron-containing inhibitors are potent serine-β-lactamase inhibitors, but the interactions of boron-based compounds with the penicillin-binding protein (PBP) β-lactam targets have not been extensively studied. We used highthroughput X-ray crystallography to explore reactions of a boroncontaining fragment set with the Pseudomonas aeruginosa PBP3 (PaPBP3). Multiple crystal structures reveal that boronic acids react with PBPs to give tricovalently linked complexes bonded to Ser294, Ser349, and Lys484 of PaPBP3; benzoxaboroles react with PaPBP3 via reaction with two nucleophilic serines (Ser294 and Ser349) to give dicovalently linked complexes; and vaborbactam reacts to give a monocovalently linked complex. Modifications of the benzoxaborole scaffold resulted in a moderately potent inhibition of PaPBP3, though no antibacterial activity was observed. Overall, the results further evidence the potential for the development of new classes of boron-based antibiotics, which are not compromised by β-lactamase-driven resistance.
An efficient, eco-friendly, base free, one-pot, sequential protocol was developed for epoxide azidolysis and copper-catalyzed azide-alkyne cycloaddition using water as the solvent for the synthesis of 3-hydroxy-1-alkyl-3-[(4-aryl/alkyl-1H-1,2,3-triazol-1-yl)methyl]indolin-2-ones. The optimized reaction conditions have been generalized in the case of aromatic as well as aliphatic alkyne partners to afford good yields and high regioselectivity.
An efficient protocol was developed for the Friedel Crafts type thioarylation for the synthesis of aromatic/heteroaromaticthioamide derivatives from aryl isothiocyanates and electron rich aromatic/heteroaromatic molecules by employing the Lewis acid AlCl3 and the less hazardous solvent cyclohexane at 70°C. The developed protocol offers advantages over the previous methods such as use of stoichiometric amount of reactants/reagent, less toxic solvent, shorter reaction time and higher yields.
Zirconocene dichloride was found to be a highly efficient catalyst for the synthesis of multi-substituted pyrroles by a three-component, one-pot reaction.
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