Chiral Siderophore Analogs: Enterobactin

Abstract

Two families of chiral enterobactin analogs, based on 1,3,5-tris(aminomethyl)benzene (TRAM) and on tris(2-aminoethyl)amine (TREN) as anchors and amino acids linking the anchor to catechol residues, have been prepared and their structures and iron(III) binding properties examined. The TRAM catechoylamides with l-leucyl (5a) and l-alanyl (5b) were found to adopt random conformations in protic solvents, while the corresponding TREN catechoylamides with l-leucyl (8a) and l-alanyl (8b) form H-bonded structures under analogous conditions. All ligands bind Fe3+ in a 1:1 stoichiometry, and most of them adopt preferentially Δ-cis configurations when l-amino acids are used, similar to enterobactin. The TREN derivative 8a was shown to be the most efficient Fe3+ ion binder so far prepared, approaching enterobactin's binding constant within less than three orders of magnitude. The superiority of the TREN derivative 8a is discussed in the light of experimental and theoretical (EFF calculations) results. Spectroscopic data include mainly the following: (i) NMR data of the protected ligands in relation to their H-bonded conformations and (ii) CD data of the Fe3+ complexes in relation to their optical purity. © 1992, American Chemical Society. All rights reserved.