Solution Conformation of Cyclic Dipeptides Having Aliphatic Side Chains

Cyclic dipeptides having aliphatic side chains, cyclo(l-Val)2, cyclo(l-Val–d-Val), cyclo(l-Leu)2, and cyclo(l-Leu–d-Leu) were synthesized and their conformation in solution was investigated by circular dichroism (CD) and proton nuclear magnetic resonance (1H NMR) spectroscopy. 1H NMR spectra in (CD3)2SO of cyclo(l-Val–d-Val) and cyclo(l-Leu–d-Leu) indicated that the diketopiperazine ring of these trans cyclic dipeptides takes a planar or a chair conformation and the molecules take a center-symmetric conformation. 1H NMR spectra in (CD3)2SO and CD spectra in CH3OH and H2O of cyclo(l-Val)2 and cyclo(l-Leu)2 indicated that the conformation of these cis cyclic dipeptides is planar-axial and flagpole-boat-type respectively. It is suggested that cis cyclic dipeptides having aliphatic side chains take such conformations in polar solvents because of the stabilization by attractive forces between aliphatic side chains.