On the double bond isostere of the peptide bond: preparation of an enkephalin analogue

Methodology for preparing dipeptide analogues in which a carbon-carbon double bond replaces the normal amide bond is described. Thus, the protected tyrosylglycine analogue, (S)-trans-5-t-butyloxycarbonylamino-6-(4-tbutoxyphenyl)hex-3-enoic acid has been synthesised and incorporated into the Leu-enkephalin analogue (3) by condensation with glycylphenylalanyl-leucine. The enkephalin analogue retained biological activity. The significance of this isosteric replacement of the amide group is discussed.