An Efficient Total Synthesis of Desferrioxamine B

Article abstract of DOI:10.1021/jo00249a001

The total syntheses of the microbial iron chelator desferrioxamine B hydrochloride and some analogues are described.The syntheric scheme is highly flexible, providing access to dihydroxamate, trihydroxamate, tetrahydroxamate, and higher homologues of desferrioxamines.The procedure also allows for access to primary amino nitrogen functionalized desferrioxamine.The scheme is predicated on the generation of the key intermediate O-benzyl-N-(4-cyanobutyl)hydroxylamine, which is acylated at the O-benzylhydroxylamine nitrogen with either succinic or acetic anhydride.The resu lting half acid amide or amide, respectively, is subjected to a series of high-yield condensations and reductions that provide desferrioxamine in 45percent overall yield.Finally a desamino analogue of desferrioxamine is prepared in order to demonstrate the synthetic utility of the scheme as applied to desferrioxamine derivatives.