Amino-acid derived benzazaboroles: structure and function of a new chemotype

Abstract

The synthesis, structural characterization, and functional properties of a series of benzazaboroles are presented. These molecules are analogues of clinically relevant benzoxaboroles and exhibit unique structural features due to a nitrogen–boron (N–B) dative bond in aqueous media. The compounds were synthesized using a reductive amination and characterized through NMR spectroscopy and X-ray crystallography. Their structures were found to be pH-dependent, transitioning between trigonal and tetrahedral boron configurations, whilst maintaining the benzazaborole five-membered ring. The benzazaboroles demonstrated selective binding to diols and saccharides, with binding affinities influenced by the length of the amino acid side chain. Fluorescence assays revealed that shorter-chain derivatives preferentially bound glucuronic and sialic acids, while longer chains favored fructose. Although antimicrobial activity was limited, antifungal effects were observed with MIC₉₀ values of 1.2 mM against Candida albicans, and one compound showed inhibitory activity against KPC-2, a class A beta-lactamase. These findings suggest the potential for further development of benzazaboroles as selective saccharide sensors, enzyme inhibitors and antifungal agents. The study provides foundational insights into the aqueous behavior and properties of this underexplored class of organoboron-containing molecules.