Synthesis of catechol- and azole-containing macrocyclic peptoids

Abstract

Metal-binding moieties such as catechol, triazole and tetrazole have been used in natural and synthetic metallophores. Researchers in various fields have investigated metal chelating abilities of these molecules. Here, we designed catechol-containing peptoids to incorporate a well-known metal-binding moiety, catechol, on a cyclic peptoid which has a moderate conformational flexibility and can offer a defined metal-binding site in solution. The design of catechol-containing cyclic peptoids was based on a metal-binding property of enterobactin, a catecholate-type siderophore in nature. Acetonide and benzyl protected catecholamines were used as submonomers for the orthogonal synthesis of catechol-containing cyclic peptoids. In addition, simple nucleophilic substitution of chlorine with azide and cyanide on a solid support was investigated, and subsequent metal-catalyzed [3+2] cycloadditions furnished triazole- or tetrazole-containing peptoids. We expect that facile synthetic pathways for catechol-, triazole- or tetrazole-containing peptoids confer chemical diversity of peptoids, and the resulting metal-binding cyclic peptoids have potential applications in the fields of catalyst development or drug discovery.