Thioacids – synthons for amide bond formation and ligation reactions: assembly of peptides and peptidomimetics

Abstract

The synthesis of α-amino thioacids and peptide thioacids and their applications in chemoselective amide bond formation, ligation of peptides/proteins/glycopeptides and synthesis of peptidomimetics are reviewed. A variety of successful methods including both C-terminal and N-terminal activations for the coupling of α-amino thioacids and peptide thioacids have ascertained the thioacid-based protocol as a benign alternative to some of the traditional methods of amide/peptide bond formation which employs carboxyl activation. In addition to the couplings involving unprotected peptide fragments and solid phase synthesis, their use in the synthesis of different classes of peptidomimetics such as thioxopeptides, imide conjugates and acylsulfonamide–peptide conjugates only illustrates the versatility of this functionality in generating diverse classes of molecules, some of which are relevant to drug discovery and chemical biology. A note on more reactive seleno counterparts of thioacids, which can be useful in selective cases, is provided.