Conformational investigation of a novel, dipeptide based molecular scaffold

The conformational features of a novel, dipeptide-based molecular scaffold are described. Four model systems of a trisubstituted 1,4-diazepine-3-one system, varying in the chirality and amino acid within the ring system, have been investigated by high-resolution NMR and metric-matrix distance geometry calculations. Because of the small number of protons within the scaffold, nuclear Overhauser effects provide only limited conformational information. Instead, extensive use of scalar ¹H-¹H and ¹H-¹³C coupling constants was utilized in the refinement. The resulting conformations of the model systems provide insight into the expected topological orientations of the amino acids or chemical functionalities attached to the seven-membered ring system, the first step of the utilization of this scaffold in the rational design of peptidomimetics.