1. Attaching Metal-Containing Moieties to β-Lactam Antibiotics: The Case of Penicillin and Cephalosporin.
- Author
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Moreno-Latorre M, de la Torre MC, Cabeza JA, García-Álvarez P, and Sierra MA
- Subjects
- Penicillins chemistry, Penicillins chemical synthesis, Molecular Structure, Models, Molecular, beta-Lactams chemistry, beta-Lactams chemical synthesis, beta Lactam Antibiotics, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Cephalosporins chemistry, Cephalosporins chemical synthesis, Coordination Complexes chemistry, Coordination Complexes chemical synthesis
- Abstract
Procedures for the preparation of transition metal complexes having intact bicyclic cepham or penam systems as ligands have been developed. Starting from readily available 4-azido-2-azetidinones, a synthetic approach has been tuned using a copper-catalyzed azide-alkyne cycloaddition between 3-azido-2-azetinones and alkynes, followed by methylation and transmetalation to Au(I) and Ir(III) complexes from the mesoionic carbene Ag(I) complexes. This methodology was applied to 6-azido penam and 7-azido cepham derivatives to build 6-(1,2,3-triazolyl)penam and 7-(1,2,3-triazolyl)cepham proligands, which upon methylation and metalation with Au(I) and Ir(III) complexes yielded products derived from the coordination of the metal to the penam C
6 and cepham C7 positions, preserving intact the bicyclic structure of the penicillin and cephalosporin scaffolds. The crystal structure of complex 28b , which has an Ir atom directly bonded to the intact penicillin bicycle, was determined by X-ray diffraction. This is the first structural report of a penicillin-transition-metal complex having the bicyclic system of these antibiotics intact. The selectivity of the coordination processes was interpreted using DFT calculations.- Published
- 2024
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