Extending the Scope of the C -Functionalization of Cyclam via Copper(I)-Catalyzed Alkyne-Azide Cycloaddition to Bifunctional Chelators of Interest.
Cédric OllierAlejandro Méndez-ArdoyFernando Ortega-CaballeroJosé L Jiménez-BlancoNathalie Le BrisPr Raphael TripierPublished in: The Journal of organic chemistry (2024)
Cyclam, known for its potent chelation properties, is explored for diverse applications through selective N -functionalization, offering versatile ligands for catalysis, medical research, and materials science. The challenges arising from N -alkylation, which could decrease the coordination properties, are addressed by introducing a robust C -functionalization method. The facile two-step synthesis proposed here involves the click chemistry-based C -functionalization of a hydroxyethyl cyclam derivative using Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). Boc-protecting groups prevent undesired copper coordination, resulting in compounds with a wide range of functionalities. The optimized synthesis conditions enable C -functional cyclams to be obtained easily and advantageously, with high application potential in the previously cited fields. The methodology has been extended to trehalose-based Siamese twin amphiphiles, enabling efficient gene delivery applications.