DNA cross-linking by a phototriggered pyrrolic progenitor developed from monocrotaline

A wide variety of pyrrolizidine alkaloids, such as monocrotaline, exert their cytotoxicity through the formation of DNA–DNA interstrand cross-links and DNA–protein cross-links. These pyrrolizidine alkaloids are oxidatively activated in vivo forming a highly reactive pyrrolic-type intermediate, which is responsible for the DNA cross-linking reaction. The oxidative pathway of activation leads to undesired toxicity. Based on a previously reported photochemically triggered progenitor of monocrotaline, we describe here the semi-synthesis and DNA cross-linking of a dicarbamate analogue of the original phototriggered progenitor.