Modular Synthesis of Triazole-Containing Triaryl α-Helix Mimetics

Abstract

We describe novel scaffold designs for nonpeptidic α-helix mimetics. The tricyclic scaffolds contain triazoles and reproduce amino acid side chains i, i+3, and i+7. The three different scaffolds are synthetically readily accessible, allow the introduction of further substituents to increase the versatility,and are suitable for library design. A modular synthesis route using Cu I- and Ru II-catalyzed azide–alkyne [3+2] cycloadditions as central steps was developed. To demonstrate the methodology, we have prepared a library of compounds containing all three scaffolds.