1,4-Diazepine-2,5-dione ring formation during solid phase synthesis of peptides containing aspartic acid β-benzyl ester

✍ Scribed by Helga Süli-Vargha; Gitta Schlosser; Janez Ilaš

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 132 KB
• Volume: 13
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.885

✦ Synopsis

Abstract

The Fmoc‐based SPPS of H‐Xaa‐Asp(OBzl)‐Yaa‐Gly‐NH~2~ sequences results in side reactions yielding not only aspartimide peptides and piperidide derivatives, but also 1,4‐diazepine‐2,5‐dione‐peptides. Evidence is presented to show that the 1,4‐diazepine‐2,5‐dione derivative is formed from the aspartimide peptide. The rate of this ring transformation depends primarily on the tendency to aspartimide and piperidide formation, which is influenced by the nature of the amino acid following the aspartic acid β‐benzyl ester (Xaa). However the bulkiness of the amino acid side chain preceeding the aspartic acid β‐benzyl ester (Yaa) is also important. Under certain conditions the 1,4‐diazepine‐2,5‐dione peptide derivative may even be formed dominantly, which is a highly undesirable side reaction in peptide synthesis, but which provides a new way for the synthesis of diazepine peptide derivatives with targeted biological or pharmacological activity. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.