Isonitrile-Based Multicomponent Synthesis of ?-Amino Boronic Acids as ?-Lactamase Inhibitors.

ABSTRACT: The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers-three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected ?-aminoboronic acids. The corresponding free ?-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by 11B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free ?-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D ?-lactamase was predicted by a molecular modeling study.

SUBMITTER: Bassini E 

PROVIDER: S-EPMC7277116 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature