Analysis of the isomerization of diketopiperazine consisting of proline and aromatic amino acid residues using nuclear magnetic resonance.

Under different concentrations of the base potassium deuteroxide KOD, the progress of reactions, such as enolization, D-substitution, isomerization, and conformational changes of diketopiperazine cyclo(L-Pro-L-Xxx) and cyclo(D-Pro-L-Xxx) (Xxx = Phe, Tyr) in DO solution, was investigated by H nuclear magnetic resonance (NMR). Cyclo(L-Pro-L-Xxx) is mostly isomerized to cyclo(D-Pro-L-Xxx) in DO solution, whereas cyclo(D-Pro-L-Xxx) is only slightly isomerized to cyclo(L-Pro-L-Xxx) even under stronger basic conditions. After adding a deuterated organic solvent (CDCOCD, CDSOCD or CDOD) to a DO solution of cyclo(L-Pro-L-Xxx), cyclo(D-Pro-L-Xxx), or increasing the temperature of the DO solution, CH-π interaction between H and the benzene ring of cyclo (D-Pro-L-Xxx) was stronger than that between H and the benzene ring of cyclo(L-Pro-L-Xxx).