Synthesis and conformational analysis of a type VIb β-turn mimetic based on an eight-membered lactam

Abstract

As part of a programme evaluating medium-ring lactams as peptide conformational constraints the trans-disubstituted lactam dipeptide (3S,8R)-3-acetylamino-8-methoxycarbamoylazocan-2-one (3) was selected as a template to mimic the type VI β-turn conformation of natural polypeptides. The enantioselective synthesis of the eight-membered lactam 3 is discussed. The X-ray crystal structure of the methyl ester precursor of 3 shows a classical type VIb β-turn conformation. Extensive ¹H NMR spectroscopic studies of the dipeptide 3 in polar solvents provided evidence for a type VI β-turn. The analysis shows an equilibrium of two folded conformations.