Synthesis and characterization of a triazine dendrimer that sequesters iron(III) using 12 desferrioxamine B groups.
The synthesis of a third generation triazine dendrimer, 1, containing multiple, iron-sequestering desferrioxamine B (DFO) groups is described. Benzoylation of the hydroxamic acid groups of DFO and formation of a reactive dichlorotriazine provide the intermediate for reaction with the second generation dendrimer displaying twelve amines. This strategy further generalizes the 'functional monomer' approach to generate biologically active triazine dendrimers. Dendrimer 1 is prepared in seven steps in 35% overall yield and displays 12 DFO groups making it 56% drug by weight. Spectrophotometric titrations (UV-vis) show that 1 sequesters iron(III) atoms with neither cooperativity nor significant interference from the dendrimer backbone. Evidence from NMR spectroscopy and mass spectrometry reveals a limitation to this functional monomer approach: trace amounts of O-to-N acyl migration from the protected hydroxamic acids to the amine-terminated dendrimer occurs during the coupling step leading to N-benzoylated dendrimers displaying fewer than 12 DFO groups.
Lim
Jongdoo
J
Department of Chemistry, Texas A&M University, College Station, TX 77843, United States.
Venditto
Vincent J
VJ
Simanek
Eric E
EE
D002614:Chelating Agents / Q000737:chemistry; D003676:Deferoxamine / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry*
D002614:Chelating Agents; D050091:Dendrimers; D014227:Triazines; D007501:Iron; D003676:Deferoxamine