Synthesis of Tri(4-formylphenyl) Phosphonate Derivatives as Recyclable Triple-Equivalent Supports of Peptide Synthesis.

To seek the novel application of organophosphorus compounds, the designed tri(4-formylphenyl) phosphonate (TFP) derivatives were successfully synthesized herein, which were used as C-terminal protecting groups of amino acid or greener triple-equivalent supports in liquid-phase peptide synthesis (LPPS). Through the support-aided precipitation effect of TFP derivatives, the peptide intermediates during peptide synthesis were separated and collected via rapid precipitation and facile filtration without chromatographic purification. Furthermore, the TFP derivative support can be directly recycled for reuse without further regeneration after being sheared from the target peptide.