Synthesis of chiral, amphiphilic, and water-soluble macrocycles via urea formation

A simple, efficient, and flexible procedure for the synthesis of chiral, amphiphilic, and water-soluble macrocycles is reported. Acylation of p-xylylenediamine with Nα-Fmoc-protected glycine, l-aspartic acid, l-glutamic acid, and l-arginine, followed by removal of Fmoc-groups, gave amino acid:p-xylylene conjugate diamines, which were converted to ten macrocycles via stepwise urea formation using p-nitrophenyl chloroformate. l-Aspartic acid-containing macrocyles proved to be soluble in aqueous buffers and a macrocycle containing four aspartate residues was found to recognize arginine and arginine esters with moderate affinity.