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

Abstract

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 (K_s) for ferric ion are from 10²³ to 10³².