Ex-Chiral Pool Synthesis of Aminooxazepinones as Conformationally Restricted b-Amino Acid Analogs

Starting from natural asparagine, an efficient synthesis of the dibenzyl protected 6-amino-1,3-oxazepin-4one (7) is reported.According to NMR based conformational studies, the lactam-bridged B-amino acid analog (7) adopts preferentially a twisted boat structure.The incorporation of the described molecular scaffold to give a constrained B-analog of the dopamine receptor modulating peptide Pro-Leu-Gly-NH, is described as an application in the field of medicinal chemistry.In search for increased target selectivity and pharmakokinetics, great efforts in peptide-based drug design are made by developing non-peptidic structural modification^.'^^Among these, lactam-bridged peptidomimetics