Unexpected Reactivity of the 9-Aminoacridine Chromophore in Guanidylation Reactions

The 9-aminoacridine chromophore is an important building
block of DNA-targeted chemotherapeutic agents. The success
of 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea as a
carrier group in cytotoxic platinum−intercalator conjugates
prompted us to explore the synthesis of an analogous
guanidine-functionalized acridine. In a successful effort to
generate such a derivative, various methods of guanidylation
were employed, which demonstrate that the acridine C9−N9 linkage is highly susceptible to electrophilic and nucleophilic attack. The newly established reactivities provide
efficient pathways to novel cyclic and spirocyclic acridine
derivatives.