A novel approach to the synthesis of cytotoxic C2–C3 unsaturated pyrrolo[2,1-c] and benzodiazepines (PBDs) with conjugated acrylyl C2-substituents

A concise synthesis of three novel C2–C3 unsaturated pyrrolo[2,1-c][1,4]benzodiazepine analogues (18–20) containing conjugated acrylyl C2-substituents is reported that utilises Heck coupling to install the C2-acrylyl side chains. These analogues possess significant cytotoxicity according to the NCI 60-cell line screen with 18 surpassing anthramycin (1) in potency.