Search for a Safe, Inexpensive and Convenient Amidation Process for Protected Amino Acids and/or Peptides

Abstract

A large class of peptide hormones contain C-terminal amides, and, as a consequence, the importance of carboxamides in biologically active peptides encouraged us to search for an efficient, inexpensive, safe and a suitable method for the amidation of protected amino acids (peptides). The general approach for the carboxamide formation involves the reaction of the amines with an activated intermediate of the corresponding acid formed by its treatment with an activating reagent. Unfortunately, not all methods involved in the conversion of acids to amides may be suitable for the synthesis of the protected amino acids (peptides) amides, possibly due to certain disadvantages associated with the use of certain activating reagents which may impair the peptide backbone. Considering these facts, and after a careful comparative study of several existing methods [1–9], a suitable amidation process for amino acids was selected and was improved for its scale-up.