Regioselective α-Peptide Bond Formation Through the Oxidation of Amino Thioacids.

Biological systems, including ribosomes and enzymes, produce peptides with an extraordinary high speed and accuracy. On the other hand, a rational and regioselective α-peptide bond formation, without involving protecting groups, is difficult to achieve in chemical synthesis. In this study, α-amino thioacids were utilized for the generation of polypeptides without using any protecting groups. We found that an α-amino thioacid could oxidatively form a diaminoacyl-disulfide moiety and undergo a subsequent intramolecular S- to N-acyl transfer to form an α-peptide bond. Even the thioacid form of lysine, which has a free ε-amino group, generated a regioselective α-peptide bond. The oxidation of amino thioacids generated the oligomers of amino acids. Interestingly, this oligomerization reaction proceeded even in the presence of iron ore, a prebiotic element, thus suggesting a plausible prebiotic peptide bond forming reaction.