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

A series of model dipeptides containing some novel axially chiral alpha,beta-didehydroamino acids at the (i + 1) position has been synthesised by reaction of the corresponding 4-(4-alkylcyclohexylidene)-2-phenyl-1,3-oxazol-5(4H)-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' beta-tum conformations. NMR spectroscopy has revealed that relatively rigid beta-tum structures also persist in solution and that the absolute configurations of the axially chiral alpha, beta-didehydroamino acids do not significantly influence the conformation of the peptide chain. Both heteroclural and homochiral dipeptides are found to accommodate the same betaII'-tum conformation. Axially chiral alpha,beta-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 alpha,beta-didehydroamino acids, the methyl, phenyl and tert-butyl groups are located about 4.3 Angstrom away from the peptide backbone in which they are incorporated. (C) 2004 Elsevier Ltd. All rights reserved.