Synthesis and evaluation of the β-turn properties of 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-ones and of their spirocyclic derivative

Abstract

A series of 4-amino-tetrahydro-2-benzazepm-3-one derivatives (Ac-Aba-Xxx-NHMe) were prepared as tetrapeptide mimetics. Considering the structural resemblance with the so-called Freidinger lactams, their propensity to adopt a β-turn conformation was investigated by NMR spectroscopy (solvent and temperature dependence) and molecular modeling. Interestingly, most of these lactams adopt extended conformations, only the spiro-benzazepinone 9 has a strong preference for the formation of a β-turn.