Synthesis of a modified carboxylate-binding pocket of vancomycin

Abstract

A 16-membered tetrapeptidic macrocycle ( 4), analog of vancomycin binding pocket, has been designed and synthesized using the efficient macrocyclisation of the corresponding linear tetrapeptide ( 14) via biaryl ether formation. In aceton, compound 4 adopted a right conformation needed for binding carboxylate anion even in the absence of N-Ac-D-Ala-D-Ala.