Hofmann degradation of asparagine and glutamine as an efficient approach for the synthesis of lysine homologues

We present a convenient and efficient approach for synthesizing lysine homologues via the Hofmann rearrangement of N-protected L-asparagine and L-glutamine. This method enabled the preparation of a diverse family of non-canonical amino acids (ncAAs) bearing side chains with varied properties, including electron-donating/accepting ability, redox activity, and fluorescence. The luminescence properties and redox behavior of these ncAAs were investigated. Furthermore, the newly synthesized Fmoc-protected ncAAs were successfully incorporated into a hexapeptide sequence using solid-phase peptide synthesis (SPPS), thus expanding the library of hexapeptide hydrogelators.