A simple route to photodynamic chlorin e6 amide derivatives

Amide derivatives of the porphyrin Ce6 have demonstrated efficacy for antimicrobial photodynamic therapy or inactivation of microorganisms. Traditional methods for their synthesis involve carbodiimide coupling agents for direct coupling or, as a more attractive option, to make key mono- and dianhydrides that are then able to react with a variety of nucleophiles. We report a process to efficiently create a Ce6 dianhydride by the simple expedient usage of acetic anhydride as both dehydrating agent and reagent. The dianhydride reacts to give mixtures of mono- and di-amide derivatives. While these are difficult to separate from each other, this route avoids the more difficult challenge of removing unreacted Ce6 from reaction mixtures. The process further avoids the need to separate undesired by-products arising from carbodiimides and provides additional benefits, as it was optimized for use with the greener solvent Cyrene. The simple reaction of acetic anhydride, as both solvent and reagent, with Ce6 leads cleanly to the dianhydride. Addition of amines leads to mixtures of mono- and diamides that are readily separated from the reaction residues.