Preparation and reactivity of aminoacyl pyroglutamates. Facile synthesis of 10‐membered‐ring cyclic dipeptides derived from 1,4‐diaminobutyric and glutamic acids

A number of protected proline-containing dipeptides Boc-Xaa-Pro-OBut were converted via epimerization-free oxidation with RuO4 to dipeptides with an internal pyroglutamic acid residue, Boc-Xaa-Glp-OBut. The latter were subjected to oxidative Hoffman-type rearrangement induced by PhI[OC(O)CF3]2 to give N-(aminoacyl)-pyroglutamates. The behavior of these derivatives under basic conditions was studied, and for two such a derivatives an aminoacyl incorporation reaction was observed, producing otherwise poorly accessible 10-membered-ring dilactams derived from 1,4-diaminobutyric and glutamic acids in practicable yields. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.