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‐<scp>L</scp>‐Leu‐OCH₃and N‐Ac‐Dehydro‐Phe‐NorVal‐OCH₃

Abstract

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 P6(5): (I) a = b = 12.528(2) A, c = 21.653(5) A; (II) a = b = 12.532(2) A, c = 21.695(4) A. The structures were determined by direct methods. Both peptides adopt similar conformations with phi,psi of dehydro-Phe as follows: (I) -57.0(5) degrees and -37.0(5) degrees; (II) -56.0(5), degrees, and -37.5(5) degrees. The observed data on dehydro-Phe when placed at the (i + 1) position show that the phi,psi values of dehydro-Phe are either -60 degrees, 140 degrees or -60 degrees, -30 degrees. The conformation of -60 degrees, 140 degrees can be accommodated only with a flexible residue at the (i + 2) position while the phi,psi values of -60 degrees, -30 degrees 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.