Aggregation modes in sheets formed by protected β-amino acids and β-peptides

Abstract

The crystal structures of four protected β-amino acid residues, Boc-(S)-β³-HAla-NHMe (1); Boc-(R)-β³-HVal-NHMe (2); Boc-(S)-β³-HPhe-NHMe (3); Boc-(S)-β³-HPro-OH (6) and two β-dipeptides, Boc-(R)-β³-HVal-(R)-β³-HVal-OMe (4); Boc-(R)-β³-HVal-(S)-β³-HVal-OMe (5) have been determined. Gauche conformations about the C^β-C^α bonds (θ~ ±60°) are observed for the β³-HPhe residues in 3 and all four β³-HVal residues in the dipeptides 4 and 5. Trans conformations (θ~180°) are observed for β³-HAla residues in both independent molecules in 1 and for the β³-HVal and β³-HPro residues in 2 and 6, respectively. In the cases of compounds 1-5, molecules associate in the crystals via intermolecular backbone hydrogen bonds leading to the formation of sheets. The polar strands formed by β³-residues aggregate in both parallel (1, 3, 5) and antiparallel (2, 4) fashion. Sheet formation accommodates both the trans and gauche conformations about the C^β-C^α bonds.