Total synthesis of the siderophore Danoxamine

The total synthesis of the linear trihydroxamate siderophore, Danoxamine, i s described. Danoxamine is a siderophore component of the naturally occurri ng siderophore-drug conjugates Salmycin A-D. The synthesis of Danoxamine fe atures a series of coupling reactions involving N-(5-benzyloxypentyl)-O-ben zylhydroxylamine being linked by a succinoyl linker to N-(benzyloxy)-1,5-pe ntanediamine. Two more succinoyl linkers and another N-(benzyloxy)-1,5-pent anediamine were used in coupling reactions to afford the fully protected si derophore. The linear tetrabenzyl-protected trihydroxamate was deprotected to afford the natural product Danoxamine.