α,β-dehydro-amino acid residues in the design of peptide structures: synthesis, crystal structure, and molecular conformation of two homologous peptides - N-Ac-dehydro-phe-L-leu-OCH3 and N-Ac-dehydro-phe-NorVal-OCH3

The dehydro-residue containing peptides N-Ac-dehydro-Phe-L-Leu-OCH3 (I) and N-Ac-dehydro-Phe-NorVal-OCH3 (II) were synthesized by the usual workup procedures. The peptides crystallize from their solutions in methanol in space group P65: (I) a = b = 12.528(2) angstrom, c = 21.653(5) angstrom; (II) a = b = 12.532(2) angstrom, c = 21.695(4) angstrom. The structures were determined by direct methods. Both peptides adopt similar conformations with φ,ψ of dehydro-Phe as follows: (I) -57.0(5)° and -37.0(5)°; (II) -56.0(5),° and -37.5(5)°. The observed data on dehydro-Phe when placed at the (i + 1) position show that the φ,ψ values of dehydro-Phe are either -60°, 140° or -60°, -30°. The conformation of -60°, 140° can be accommodated only with a flexible residue at the (i + 2) position while the φ,ψ values of -60°, -30° are obtained with a bulky residue at the (i + 2) position as in the present structures. The molecules are packed in a helical way along the c axis. These are held by two strong intermolecular hydrogen bonds involving both NH as donors and acetyl group and dehydro-Phe oxygen atoms as acceptors.