THE SYNTHESIS OF 6-AMINO-5-OXO-7-PHENYL-1,4-OXAZEPINES AS CONFORMATIONALLY CONSTRAINED GAUCHE (-) DIPEPTIDE MIMETICS

6-Amino-5-oxo-7-phenyl-1,4-oxazepines were synthesized from beta-phenylserine by a versatile route to provide gauche (-) phenylalanyl-X dipeptide mimetics(1a-h). NMR was utilized to elucidate the solution conformation of the protected mimetics. The seven membered ring was found to be in a chair conformation with the phthalimide moiety and the phenyl ring pseudo-equatorial, consistent with the gauche (-) conformation (dihedral angle X1=-60-degrees). Dipeptide mimetic 2 was synthesized from 1a to probe the effect of the gauche (-) conformation on the inhibition of metalloproteinases. These gauche (-) dipeptide mimetics may be useful tools for the investigation of conformational preferences of enzyme substrates and receptor ligands.