SULFONATED CATECHOLAMIDE ANALOGS OF ENTEROBACTIN AS IRON SEQUESTERING AGENTS

The treatment of certain genetic diseases, such as /3- thalassemia major (Cooley's anemia), requires chronic transfusion therapy.1-2 This produces a secondary hemochromatosis, which eventually results in the failure of vital organs due to buildup of iron in the tissues, and the death of most patients by early adulthood. Since there is no physiological mechanism in man for the removal of iron, the treatment of iron overload must rely on chelating agents which can effect iron excretion, the development of which is now the goal of a major program.3 We have shown that the siderophore (microbial iron-transport agent4,5) enterobactin (1) is the most powerful iron(III) chelating agent known to date.6,7 While enterobactin is itself not a suitable candidate as an iron-chelating drug, other 2, 3-dihydroxybenzoylamides are good candidates, and we have previously reported the preparation of 1, -5, 9-N, N', N“-tris(2,3-dihydroxybenzoyl)cyclotriazatridecane (2) and 1,3,5-N, N', N“-tris(2,3-dihydroxybenzoyl)triaminomethylbenzene (3) (Chart I).8-11 Thermodynamic9 and biochemical12 studies of these compounds have shown them to be very powerful chelating agents for ferricion. © 1979, American Chemical Society. All rights reserved.