A New Wave of Amide Bond Formations for Peptide Synthesis

Abstract

The construction of peptidic amide bonds has become a daily laboratory practice by virtue of well-established ‘coupling reagents’. Nonetheless, inherent limitations connected to these classical coupling methods in terms of waste, safety and expense have yet to be conquered. Research efforts have been devoted to synthetic methods able to surpass these limitations. This short review focuses on the advances made in these ‘non-classical’ methods for amide bond formation with a specific application in peptide chemistry. It consists of two main sections: (i) novel carboxylic activation reagents, and (ii) carboxylic acid and amine surrogates.1 Introduction2 Alternative Carboxylic acid Activation Reagents3 Carboxylic Acid and Amine Surrogates4 Conclusion and Perspectives

Tantalum-Catalyzed Amidation of Amino Acid Homologues

“…However, the coupling-reagent-mediated CO–NH bond formation methodologies usually require large amounts of reaction solvents and typically suffer from racemization problems in addition to the production of chemical waste related to the coupling reagents . A catalytic version of the amide bond formation between carboxylic acids and amines has attracted considerable attention in the last quarter century, and several metal catalysts have been developed for this transformation. , However, most of these metal-catalyzed amidations require high temperatures and use of a Dean–Stark trap and/or molecular sieves , for promoting the conversion of the hydroxy group into an active leaving group by removal of water. Furthermore, these approaches can sometimes cause racemization challenges during peptide synthesis.…”

Novel Methodologies for Chemical Activation in Organic Synthesis under Solvent-Free Reaction Conditions

“…Peptides have interesting properties, not just as catalysts for many metabolic reactions but also as pharmacological and biological agents. It is therefore not surprising that a significant number of synthetic chemists are working actively to develop "greener" methodologies for the synthesis of both natural and unnatural peptides [65][66][67][68][69][70][71][72][73].…”

Synthesis of Some Analogues of Polymyxin E1 Antibiotic Using Automated Solid Phase Peptide Synthesis Assisted With Microwave Irradiation

“…Scheme (1) shows the schematic synthetic steps performed for two analogues as a reference for each cyclization technique (analogue I for cyclization in solution (left) and analogue IV (right) for cyclization on polymeric support. In this work, the use of different coupling agents [38] was also investigated. Cyclization was performed using three different coupling reagents, EDC.HCl condensing agent in case of analogues (I-II), BOP in case of analogue (III) and DIC condensing agent in case of analogues (IV-V) under heterogenous conditions.…”