Extending the scope of the C-functionalization of cyclam via Copper(I)-catalyzed Alkyne-Azide Cycloaddition to bifunctional chelators of interest

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, that 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.