Experimental and theoretical investigations on the folding modes of depsipeptide molecules

The coupling of N‐acyl‐α‐amino‐acids with α‐hydroxyacid‐methyl amides results in depsipeptide molecules containing two chiral centers and one ester function inserted between two amide functions. Their conformational features have been investigated by IR spectroscopy, proton magnetic resonance, X‐ray diffraction, and theoretical P.C.I.L.O. calculations. It is shown that most of these molecules are folded by an intramolecular 4 → 1 hydrogen bonding. Two folded conformations, similar to the well known β turn in peptides, are described, the stability of which depends on the configurational sequence in the investigated molecule. LL and LD species are folded in two different ways whereas LG sequences containing an achiral hydroxy‐acid residue accommodate both of them. The presence of a N‐terminal achiral amino acid noticeably decreases the folding ratio. The above conclusions are then compared with the conformational features of homologous tripeptide molecules.