2-Azidoethoxy derivatives of 2-aminocyclohexanecarboxylic acids (ACHC): interesting building blocks for the synthesis of cyclic β-peptide conjugates

Oligomers of cyclic-β-aminoacids possess a high resistance to peptidase-catalyzed hydrolysis and display a high intrinsic tendency to adopt regular secondary structures. These characteristics are attractive to develop new biologically active substances. However, cyclic-β-peptides often show limited solubility in water and cannot be conjugated to biologically relevant fragments, such as oligosaccharides, which are often essential for full biological activity of natural α-peptides. In this article, we report the synthesis of one trans- and one cis-2-aminocyclohexanecarboxylic acid (ACHC), both functionalized with a hydroxy group, to increase the solubility in water, and an azidoethoxy group to allow the synthesis of cyclic-β-peptide conjugates by a ‘click reaction’.