Reaction mechanisms in peptide synthesis. Part 2. Tautomerism of the peptide bond

✍ Scribed by Jerzy Ciarkowski; Francis M. F. Chen; N. Leo Benoiton

• Book ID: 104635836
• Publisher: Springer Netherlands
• Year: 1991
• Tongue: English
• Weight: 876 KB
• Volume: 5
• Category: Article
• ISSN: 0920-654X
• DOI: 10.1007/bf00135317

✦ Synopsis

We had concluded in previous work that ring opening of a 2-alkyl-5(4H)-oxazolone by water or ammonia leads to transient high-energy imidol intermediates which instantly tautomerize to the native amides. Using the MOPAC molecular orbital program, detailed geometric and energetic characteristics of the tautomerism of a peptide bond have been determined on the AM 1 level. The results demonstrate that tautomerism of a peptide bond comprises a three-stage process involving three successive transition states and a bimolecular mechanism: (1) E~Z peptide bond isomerization followed by dimerization, (ii) concerted double-hydrogen exchange leading to an a-hydroxyimine (imidic acid) followed by splitting of the dimer, and (iii) Z~E Nmethylimine reversion. While pathway (iil-~ii~i) is predicted as a feasible route terminating in the formation of a peptide bond, the inverse route (nl~-ii~i) is excluded as a possible initial step in the generation of a 5(4H)-oxazolone intermediate.