Structure of N-tert-butyloxycarbonyl-D-leucyl-L-phenylalanylethanolamide. An N alpha-protected analogue of the COOH-terminal dipeptide of linear gramicidins.

Abstract

Solid state conformational analysis of N-tert-butyloxycarbonyl-D-leucyl-L-phenylalanylethanolamide (t-Boc-D-Leu-L-Phe-EA), an N alpha-protected analogue of the COOH-terminal dipeptide of linear gramicidins, carried out by x-ray diffraction, has indicated that the molecules are characterized by an N-H...O = C intramolecularly hydrogen-bonded chain reversal of the beta-turn II' type. One of the two independent molecules in the asymmetric unit shows an additional intramolecular hydrogen bond of the O-H...O = C type, linking the hydroxyl function of the COOH-terminal ethanolamide moiety to the carbonyl oxygen of the urethane N-protecting group. This is the first experimental evidence for a beta-turn conformation fused with the oxy analogue of an alpha-turn. The results of an investigation in a solvent of low polarity (deuteriochloroform), using infrared absorption and 1' nuclear magnetic resonance, strongly support the view that an intramolecularly hydrogen-bonded beta-turn conformation is the most populated conformation of t-Boc-D-Leu-L-Phe-EA molecules at high dilution. In the self-association process, taking place at high concentration, the urethane and peptide NH groups are involved as hydrogen-bonding donors.