Stereospecific synthesis of conformationally constrained γ-amino acids: New foldamer building blocks that support helical secondary structure

(Figure Presented) A highly stereoselective synthesis of novel cyclically constrained γ-amino acid residues is presented. The key step involves organocatalytic Michael addition of an aldehyde to 1-nitrocyclohexene. After aldehyde reduction, this approach provides optically active β-substituted δ-nitro alcohols (96-99% ee), which can be converted to γ-amino acid residues with a variety of substituents at the α position. We have used these new building blocks to prepare α/γ-peptide foldamers that adopt a specific helical conformation in solution and in the solid state.