Abstract/Summary

In this study, we have developed a highly enantioselective organocatalytic route to the (1S,2R)-2-(aminomethyl)cyclopentane-1-carboxylic acid monomer precursor, which has a cis-configuration between the C- and N-termini around the cyclopentane core. Kinetic measurements show that the product distribution changes over time due to epimerization of the C1 center. Computations suggest the cis-selectivity is a result of selective C-C bond formation, whilst subsequent steps appear to infuence the selectivity at higher temperature. The resulting gamma-amino acid residue was incorporated into a novel gamma/alpha-peptide which forms a well-ordered 10/12-helix with alternate H-bond directionality in spite of the smallest value of the zeta-angle yet observed for a helix of this type. This highly dened structure is a result of the narrow range of potential zeta-angles in our monomer. In contrast, the larger range of potential zeta-values observed for the corresponding trans-system can be fulfilled by several competing helical structures.