Combinatorial Syntheses of Polyhydroxamate Siderophores: Desferrioxamine, Exochelin, Mycobactin, and Aerobactin Libraries

Siderophores are natural products, often containing amino acid derivatives, that are produced by microorganisms to chelate ferric ion as part of an iron-uptake system essential for survival. In order to explore several therapeutic opportunities, we have developed a combinatorial synthetic strategy to prepare libraries of analogs of a number of different siderophores, including desferrioxamine (DFO), for potential treatment of iron overload [1]; and exochelin, mycobactin and aerobactin for potential antibiotic applications. These siderophores all contain hydroxamate groups as primary coordination sites for the ferric ion (Figure 1). Their typical stability constants (Ks) for ferric ion are from 1023 to 1032.