Selective functionalization at the small rim of calix[6]arene. Synthesis of novel non-symmetrical N3, N4 and N3ArO biomimetic ligands

Eight novel calix6]arene-based biomimetic ligands for transition metal ions have been synthesized. They display a non-symmetrical N₃, N₄ or N₃ArO binding core that mimics enzyme active sites presenting histidine and tyrosine residues. The key step for their synthesis is the mono-alkylation at the small rim of the C_3v symmetrical trimethyl ether derivative of tBu-calix6]arene with N-Boc-2-chloroethylamine to yield a novel calix6]arene synthon. Its combined O-alkylation with a chloromethyl aromatic amine and N-deprotection or alkylation or reductive alkylation with a salicylaldehyde derivative yielded the calix6]arene-based ligands with mixed N/O donors.