Formation of pyroglutamylglutamine (or asparagine) diketopiperazine in ‘non‐classical’ conditions: a side reaction in peptide synthesis

Abstract

Formation of by-products pyroglutamylglutamine diketopiperazine (5a) or pyroglutamylasparagine diketopiperazine (5b) were observed during the condensation of pyroglutamic acid active ester with C-protected glutaminyl(or asparaginyl)-proline derivatives. Successful synthesis of Glp-Gln(or Asn)-Pro-derivatives is possible after coupling of Glp-Gln(or Asn)-OH with proline-derivatives.