Microbial Iron Chelators: Total Synthesis of Aerobactin and Its Constiruent Amino Acid, N6-Acetyl-N6-hydroxylysine

Article abstract of DOI:10.1021/ja00375a025

The synthesis of the natural ferric ionophore (-)-aerobactin (1) and of its constituent amino acid N⁶-acetyl-N⁶-hydroxylysine (2) is described.The benzyl hydroxamates * and ( were subjected to triphenylphosphine-diethyl azodicarboxylate-mediated alkylations with the ε-hydroxynorleucine derivative 7a.While * gave a complex mixture with predominant carbonyl O-alkylation, 9 was cleanly N-alkylated to yield 14.Compounds 10a,b were prepared by direct alkylation of 8 with bromides 15a,b which gave predominant N-alkylation.Hydrogenation of (D,L)-10a yielded (D,L)-N-⁶- acetyl-N⁶-hydroxylysine (2).Optically active 10b, prepared from (L)-ε-hydroxynorleucine, was α-N deprotected and coupled with anhydromethylenecitryl chloride (18) to yield 19, which was deprotected in two steps to yield (-)-aerobactin (1).