%0 Journal Article
%A Kortman, Hannah M.
%A Fang, Hao
%A Bastick, Kane A. C.
%A Völkel, Charlotte
%A Oberthür, Dominik
%A Seeberger, Peter H.
%A Perbandt, Markus
%A Molloy, John J.
%T Fused 3D boron heterocycles via EnT catalysis: synthesis, modification and validation as beta-lactamase inhibitors
%J Chemical science
%V 17
%@ 2041-6520
%C Cambridge
%I RSC
%M PUBDB-2025-05386
%P 10.1039.D5SC05518K
%D 2026
%Z cc-by
%X The installation of a boron unit into bioactive scaffolds continues to unlock novel modes of molecular recognition in drug discovery. As such, de novo strategies to access 3D boron-containing frameworks, that modulate the intrinsic reactivity at boron, are being intensively pursued. Herein, we report a visible light-mediated energy transfer (EnT) catalysis strategy that enables the [2 + 2] cycloaddition of boron-containing heterocycles to construct 3D frameworks with high structural complexity. Leveraging both inter- and intramolecular cycloadditions, a suite of angularly fused boron heterocycles was accessed, offering enhanced steric shielding and modular handles for additional interactions. A boron deletion strategy permits the synthesis of benzofuran scaffolds, otherwise inaccessible via direct EnT. Crucially, the resulting 3D architectures mimic structural motifs found in the potent β-lactamase inhibitor Xeruborbactam. The biological relevance of these frameworks was validated by NMR titration, pKa analysis, and co-crystallisation with serine β-lactamase CTX-M-14, revealing enantiospecific binding and a well-defined hydrogen bonding network. These results establish a versatile platform for the synthesis of functionalised boron heterocycles with direct translational potential in medicinal chemistry.
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1039/D5SC05518K
%U https://bib-pubdb1.desy.de/record/642190