Synthesis and conformational properties of model dipeptides containing novel axially chiral α,β-didehydroamino acids at the ( i+1) position of a β-turn conformation

Abstract

A series of model dipeptides containing some novel axially chiral α,β-didehydroamino acids at the ( i+1) position has been synthesised by reaction of the corresponding 4-(4-alkylcyclohexylidene)-2-phenyl-1,3-oxazol-5(4 H)-one with ( S)-phenylalanine cyclohexylamide. The conformations of two dipeptides in the crystal state have been studied by X-ray diffraction crystallographic analysis. The backbone torsion angles suggest that both peptides adopt similar type-II′ β-turn conformations. NMR spectroscopy has revealed that relatively rigid β-turn structures also persist in solution and that the absolute configurations of the axially chiral α,β-didehydroamino acids do not significantly influence the conformation of the peptide chain. Both heterochiral and homochiral dipeptides are found to accommodate the same βII′-turn conformation. Axially chiral α,β-didehydroamino acids ( R a )- and ( S a )-4-methyl-, 4-phenyl- and (4- tert-butylcyclohexylidene)glycine can be considered as elongated structural analogues of alanine, phenylglycine and tert-leucine of R and S configuration since, in these chiral α,β-didehydroamino acids, the methyl, phenyl and tert-butyl groups are located about 4.3 Å away from the peptide backbone in which they are incorporated.