Peptide Bond Formation through Fragment Condensation with Silylating Reagents

In the context of peptide bond formation, the condensation of peptide fragments facilitates parallel synthesis, thereby streamlining the process and representing an efficient strategy that is unique to liquid-phase chemistry. However, this approach often results in epimerization of the stereocenter adjacent to the activated carboxylic acid due to the formation of oxazolones. The epimerization-free formation of peptide bonds is therefore crucial for the synthesis of peptide drugs. In this study, peptide bonds were formed between peptide fragments with minimal epimerization using HSi(OCH(CF₃)₂)₃ as the silylating reagent. This method was applicable to various peptides bearing diverse functional groups and enabled the synthesis of octapeptides. This strategy holds potential for application in pharmaceutical drug development and in the synthesis of bioactive natural products.