Structural highlights
Publication Abstract from PubMedThe 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 beta-lactamase inhibitor Xeruborbactam. The biological relevance of these frameworks was validated by NMR titration, pK (a) analysis, and co-crystallisation with serine beta-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. Fused 3D boron heterocycles via EnT catalysis: synthesis, modification and validation as beta-lactamase inhibitors.,Kortman HM, Fang H, Bastick KAC, Volkel C, Oberthur D, Seeberger PH, Perbandt M, Molloy JJ Chem Sci. 2025 Nov 3;17(1):247-254. doi: 10.1039/d5sc05518k. eCollection 2026 Jan , 7. PMID:41221109[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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