Macrocyclic catechol-containing ligands

Abstract

Tri-catechol ligands form selective and strong complexes with the ferric ion, making them attractive candidates for use as iron decorporation pharmaceuticals. Recent work in our group has concentrated on the synthesis of macrocyclic and macrobicyclic ligands incorporating the 2,3-dihydroxyterephthalamide binding subunit, which has been shown to be the most efficient bidentate iron chelator known (pM' ‘s ranging from 21.1 to 22.7). Macrocyclic polycatechol ligands with endocyclic binding subunits were synthesized using high dilution techniques in yields of up to 24%. A series of macrobicyclic tri-catechol ligands in which the ligand properties were varied by incorporating TREN, mesitylene triamine, and TPT backbones, were synthesized in 10-15% yield via a stepwise approach employing high dilution conditions for the tripod-tripod coupling cyclization. In addition, a template synthesis was developed which allowed the preparation of (Et3NH)3[Fe(bicapped TRENCAM)] in 50% overall yield. Reversible electrochemical behavior was observed above pH 11.5 for Na3[Fe(bicapped TRENCAM)] (E1/2 —.95V vs. NHE) and above pH 8.3 for Na3[Fe(bicapped TRENMECAM)] (E1/2 —.92 V. vs. NHE). The crystal structure of Na3[Fe(bicapped TRENCAM)] was determined and showed the coordination geometry about the metal center to be trigonal prismatic, an unprecedented geometry for Fe(III). © 1988 IUPAC