Ribosomally-synthesized peptides and proteins are derived from a core set of 20 canonical amino acids. However, the vast structural and functional diversity that is observed in peptide natural products is largely attributed to post-translational modifications of both the amino acid side-chains and the peptide backbone, which alter the structure, and by extension the function of these biomolecules.1 In order to replicate these precise peptide modifications in a laboratory setting, synthetic methods must be devised that allow for the targeted modification of specific amino acids in a generalizable way.
Here, we introduce a novel class of amino acid-derived sulfinate salts, which under mild oxidative conditions, act as a source of alkyl radicals amenable to divergent functionalization.2-3 The synthesis of four amino acid sulfinates derived from serine, threonine, hydroxyproline and homoserine is described and their reactivity with a variety of different radical traps including heteroaromatics and disulfides is probed. This desulfinylative coupling is examined under chemical, photochemical and electrochemical oxidation conditions. In addition, we demonstrate the incorporation of an orthogonally-protected sulfinate precursor into a peptide substrate, demonstrating the potential application of this chemistry for direct mimicry of post-translational modifications. With the broad range of potential applications, this chemistry could serve to simplify the synthesis of post-translationally modified peptide natural products.