Natural-Product-Directed Catalytic Stereoselective Synthesis of Functionalized Fused Borane Cluster–Oxazoles for the Discovery of Bactericidal Agents

Abstract

The identification of an alternative chemical space in order to address the global challenge posed by emerging antimicrobial resistance is very much needed for the discovery of novel antimicrobial lead compounds. Boron clusters are currently being explored in drug discovery due to their unique steric and electronic properties. However, the challenges associated with the synthesis and derivatization techniques of these compounds have limited their utility in the rapid construction of a library of molecules for screening against various biological targets as an alternative molecular platform. Herein, we report a transition-metal-catalyzed regioselective direct B–H alkylation–annulation of the closo-dodecaborate anion with natural products such as menthol and camphor as the directing groups. This method allowed the rapid construction of a library of 1,2,3-trisubstituted clusters, which were evaluated in terms of their antibacterial activity against WHO priority pathogens. Several of the synthesized dodecaborate derivatives displayed medium- to high-level bactericidal activity against Gram-positive and Gram-negative bacteria.