Convergent Synthesis of Macrocyclic and Linear Desferrioxamines

Abstract

Polyhydroxamate desferrioxamines (DFO) are nontoxic siderophores endowed with high potential for development of therapeutic chelating agents. Herein, we report a modular and convergent strategy for diverse synthesis of macrocyclic and linear DFOs. The strategy employed orthogonally protected N‐hydroxy‐N‐succinylcadaverine building blocks, which allowed bidirectional extension of the DFO structure. The efficiency of the new strategy was demonstrated by the total synthesis of 44‐membered macrocyclic DFO‐T1, as well as four related DFO compounds in 11–13 linear steps and 2.1 %–10 % overall yields. Comparison of the iron binding affinity of the DFOs revealed DFO‐E as the best chelator.