A new method for amide bond formation

© 2016 Dr. Aysa PourvaliThe synthesis of amide bonds is one the most important issues in organic chemistry. The reaction of thioamides and silver carboxylates to generate imides, and ultimately amide bonds, was investigated. This system was shown to be effective for the coupling of a range of N-protected amino acids with amino acid derived thioamides, leading to the preparation of dipeptide imides. Selective cleavage of the imide compounds by methanolysis or hydrolysis was shown to be a viable general method for amide bond formation. However, the described method was not suitable for the generation of polypeptides by coupling peptide acids with peptide N-thioacetamides. Nevertheless, the synthesis of polypeptides could be achieved by coupling of a peptide containing a free C-terminal carboxylic acid to an amino ester thioamide in the presence of silver(I), which after imide hydrolysis and ester deprotection gives the homologated peptide. This cycle is repeatable to synthesize longer polypeptides. The application of our method to synthesise polypeptides was exemplified by the synthesis of the pentapeptide thymopentin. The synthesis was performed in the N→C direction, without any epimerization. Initial investigations towards the synthesis of cyclopeptide alkaloids in the presence of Ag2CO3 were also undertaken