posted on 2022-02-11, 17:38authored byRajesh Varkhedkar, Fan Yang, Rakesh Dontha, Jianglin Zhang, Jiyong Liu, Bernhard Spingler, Stijn van der Veen, Simon Duttwyler
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.