TY  - JOUR
AU  - Kortman, Hannah M.
AU  - Fang, Hao
AU  - Bastick, Kane A. C.
AU  - Völkel, Charlotte
AU  - Oberthür, Dominik
AU  - Seeberger, Peter H.
AU  - Perbandt, Markus
AU  - Molloy, John J.
TI  - Fused 3D boron heterocycles via EnT catalysis: synthesis, modification and validation as beta-lactamase inhibitors
JO  - Chemical science
VL  - 17
SN  - 2041-6520
CY  - Cambridge
PB  - RSC
M1  - PUBDB-2025-05386
SP  - 10.1039.D5SC05518K
PY  - 2026
N1  - cc-by
AB  - 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.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1039/D5SC05518K
UR  - https://bib-pubdb1.desy.de/record/642190
ER  -