Synthesis and Characterization of Adamantane‐Containing Heteropeptides with a Chirality Switch

Oligomers assembled from designed building blocks to fold in novel ways have emerged as tools and allow the creation of new structures and molecular properties. Herein, we describe the use of a highly constrained adamantane moiety with one amino group and three carboxylic acids as a monomer. It can be viewed as a constrained, alpha,alpha-dialkylated gamma-amino tri-acid with side-chains that mimic glutamic acid. We alternated this amino acid with glycine to synthesize a heteropeptide adamantane-based oligomer. An N-terminal l- or d-tyrosine was included to investigate possible chirality induction. The oligomer was assembled by solid-phase peptide synthesis using Fmoc- and Boc-protection strategies. This novel oligomer was characterized by circular dichroism spectroscopy, which revealed a clear effect from the chirality of the N-terminal tyrosine. Molecular dynamics simulation indicated that the adamantane oligomers populated compact conformations, with a subset forming cyclic geometries by hydrogen bonding. Through these interactions the chirality of Tyr induced an overall chirality in the cyclic conformations, which is in agreement with the spectroscopic data. This points to the use of adamantane building blocks in novel chirality switches.