Synthetic enterobactin analogs. Carboxamido-2,3-dihydroxyterephthalate conjugates of spermine and spermidine

Two examples of a new class of synthetic polycatecholate ligands, the carboxamido-2,3-dihydroxyterephthalate conjugates of spermine (8) and of spermidine (10), have been synthesized via the generally useful synthon methyl-2,3-dimethoxyterephthaloyl chloride (6). Initial biological evaluation reveals tetrameric terephthalate (8) to be an extremely effective agent for sequestering and removing plutonium from mice; a single 25-mumol/kg (ip) dose of 8 removed 73% of the plutonium citrate previously injected (iv, 1 h earlier). Under the same conditions, trimeric terephthalate (10) excreted only 49% of injected plutonium. In vitro kinetic experiments have shown that 10 rapidly and quantitatively removed Fe from human transferrin. These results are discussed in relation to the design of metal-ion specific sequestering agents.