Electrolytic Macrocyclizations: Scalable Synthesis of a Diazonamide-Based Drug Development Candidate

An electrochemical method to synthesize the core macrolactam of diazonamides is described. Large ring‐forming dehydrogenation is initiated by anodic oxidation at a graphite surface. The reaction requires no tailoring of the substrate and occurs at ambient temperature in aqueous DMF in an undivided cell open to air. This unique chemistry has enabled a concise, scalable preparation of DZ‐2384; a refined analog of diazonamide A slated for clinical development as a cancer therapeutic. Electrifying chemistry! The core macrolactam of diazonamides can be synthesized electrochemically. This large ring forming dehydrogenation has enabled a concise preparation of DZ‐2384, a refined analogue of diazonamide A slated for clinical development as a cancer therapeutic.