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.
Ma
Zhidong
Z
Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
Day
Cynthia S
CS
Bierbach
Ulrich
U
D000585:Aminacrine / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D006147:Guanine; D000585:Aminacrine; D004247:DNA; C427203:calf thymus DNA