Journal Article

PUBDB-2025-05386

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Fused 3D boron heterocycles via EnT catalysis: synthesis, modification and validation as beta-lactamase inhibitors

Kortman, H. M. ; Fang, H. ; Bastick, K. A. C. ; Völkel, C. ; Oberthür, D.CFEL*XFEL.EU*DESY* ; Seeberger, P. H. ; Perbandt, M.Extern*XFEL.EU* ; Molloy, J. J. (Corresponding author)

2026
RSC Cambridge

This record in other databases:  

Please use a persistent id in citations: doi:10.1039/D5SC05518K  doi:10.3204/PUBDB-2025-05386

Abstract: 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.

Note: cc-by

---

Contributing Institute(s):

1. CFEL-1 (HH_FS_CFEL-1)
2. CFEL-Coherent X-Ray Imaging (FS-CFEL-1)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. DFG project G:(GEPRIS)431232613 - SFB 1449: Dynamische Hydrogele an Biogrenzflächen (431232613) (431232613)
3. FS-Proposal: BAG-20230677 (BAG-20230677) (BAG-20230677)

Experiment(s):

1. PETRA Beamline P11 (PETRA III)

Appears in the scientific report 2026

---

Database coverage:
; ; ; ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; IF >= 5 ; Index Chemicus ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---