Simple synthesis and functionalization of α-hydroxyglycine-containing peptide fragments.

α-Hydroxyglycine (α-OH-Gly) is a naturally occurring amino acid that is also a versatile synthon for accessing non-natural amino acids. However, current synthetic routes to this moiety require conditions that are incompatible with reactive amino acid side chains and their accompanying protecting groups needed for peptide synthesis. We report here a method for the chemical synthesis of Fmoc-protected α-OH-Gly-containing dipeptides. Our method features operational simplicity and is compatible with protecting groups needed for peptide synthesis. The utility of this method is then demonstrated through substitution at the α-OH-Gly position to yield myriad non-natural amino acid-containing dipeptide fragments. By addressing this gap in capability, we were able to incorporate this moiety into peptide fragments and functionalize this site to rapidly generate complex peptide components that can be readily integrated into larger structures.