Total Syntheses of Agelamadin F and (±)‐Tauroacidin A, Enabled by NaClO ₂ ‐Mediated Coupling Reactions of Oroidin and Amines

Agelamadin F and tauroacidin A are pyrrole-imidazole alkaloids isolated from marine sponges. To the best of our knowledge, no methodology has been established for the oxidative installation of amine or pyridine moieties at the C15 position of oroidin, except for our previous total synthesis of mauritamide B, in which C15 was modified with taurine under an oxidative condition using activated carbon and molecular oxygen. In this study, we report a more effective condition for oxidative C─N coupling; sodium chlorite enables the incorporation of a broader range of amines at the C15 position of oroidin. Using this oxidant, we achieved the first total syntheses of agelamadin F and tauroacidin A, even though in low yields. In addition, nine C15-N-amino acid-substituted oroidin derivatives were successfully prepared to demonstrate the applicability and versatility of this oxidative coupling reaction. Based on the structures of the products, we propose that a key structural requirement for the nucleophilic amines to react in this coupling reaction is the ability to form zwitterionic species after reaction with oroidin.