2-Aminopropane-1,2,3-tricarboxylic acid: Synthesis and co-crystallization with the class A β-lactamase BS3 of Bacillus licheniformis

The title compound 4 has been prepared in four steps from ethylglycinate in 63% overall yield. This amino analog of citric acid has been co-crystallized with the class A β-lactamase BS3 of Bacillus licheniformis and the structure of the complex fully analyzed by X-ray diffraction. Tris-ethyl aminocitrate 3 and the free tris-acid 4 have been tested against a member β-lactamase from all distinct subgroups. They are novel inhibitors of class A β-lactamases, still modest but more potent than citrate and isocitrate.

Graphical abstractSynthesis and biochemical evaluation against β-lactamases of amino bioisoter of citric acid are presented. The structure of the complex aminocitrate-BS3 has been analyzed by X-ray diffraction and compared to ones with citrate and isocitrate.Figure optionsDownload full-size imageDownload as PowerPoint slide