Studies on amino acids and peptides. Part 6. Methods for introducing thioamide bonds into the peptide backbone: synthesis of the four monothio analogues of leucine enkephalin

Backbone-modified oligopeptidic bioregulators. The synthesis and configuration of thioamide, amidoxime, cyanoamidine, and amidrazone analogs of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe-OR)

“…W e have already described appropriate methodologies (3), preferable to previous ones (4) for reasons previously outlined, for the selective incorporation of thioamide functions (5) into peptide backbones and have recently illustrated the effects of such modifications on the pharmacological properties of the endogenous opiate Leu5-enkephalin (6). The results of a similar study by others (7) have also been divulged and are in general concordance with ours. W e now wish to describe an extension of our methodology for thiopeptide formation and to illustrate the use of the thioamide function (2) (Scheme I) as the precursor of novel backbone analogs where the sulfur is replaced by substituted nitrogen functions (3).…”

Post-assembly Peptide Modifications by Chemical Methods

“…Since most of the peptide isosteres are synthesized by the traditional peptide synthesis methodologies, this aspect is not discussed in detail. Interested readers may refer to the references [94][95][96][97][98][99][100][101][102][103][104][105][106][107][108] cited in the reference section.…”

An imidazoline pseudodipeptide suitable for solid phase peptide synthesis

“…Reaction with Lawesson's reagent (toluene, reflux) readily yielded the corresponding thioamide 8 (80%), [h] D 20 + 29.0 (c = 1.0, EtOH), and S-alkylation of this thioamide was accomplished in neat iodomethane at reflux [11]. The thioimidate salt 9 so produced was not stored but was prepared as required and used directly, in order to minimize loss through hydrolysis, etc.…”