Synthesis and Investigation of a Chiral Enterobactin Analogue Based on a Macrocyclic Peptide Scaffold

摘要

A chiral C-3-symmetric enterobactin analogue (1) has been synthesized by attachment of three 2,3-dihydroxybenzoyl units to a chiral oxazole-containing macrocyclic peptide scaffold. Complex formation kinetics and stoichiometry with various metal ions were investigated by spectrophotometric methods. In the cases of Al-III, In-III and Fe-III complexes, UV absorption and CD kinetics showed nonlinearity, which results from slow conformational changes of the octahedral complexes. Virtual binding constants were determined from UV absorption data and showed selective binding of Ga-III in preference to Fe-III, by two orders of magnitude. CD spectroscopy revealed highly diastereoselective binding of Al-III, Ga-III, In-III, Fe-III and Ge-IV ions at the helical chirality opposite to that of the analogous enterobactin complexes. Ab initio calculations confirmed the energetic stabilization of the Lambda isomers relative to the Delta isomers.