Selective Stepwise Arylation of Unprotected Peptides by Pt^IV Complexes

Area of Science:

• Organometallic Chemistry
• Peptide Chemistry
• Synthetic Organic Chemistry

Background:

• Peptide modification is crucial for developing new therapeutics and functional materials.
• Selective functionalization of unprotected peptides remains a significant challenge in synthetic chemistry.

Purpose of the Study:

• To develop a novel method for the selective arylation of unprotected peptides.
• To explore the utility of Platinum(IV) complexes in peptide modification.

Main Methods:

• Synthesis of Platinum(IV) fluoride complexes with a bulky bidentate phosphinophenoxide ligand.
• Application of these complexes for the arylation of X-H (X=S, N) bonds in unprotected peptides.
• Stepwise addition of complexes for one-pot sequential arylation.

Main Results:

• The Platinum(IV) complexes exhibited excellent reactivity and selectivity in arylation reactions.
• Successful arylation of Cys, N-terminus, Lys, and Trp residues was achieved under mild, including aqueous, conditions.
• A one-pot procedure for introducing multiple aromatic groups onto peptides was established.

Conclusions:

• The developed Platinum(IV) complexes provide a powerful tool for the selective and efficient arylation of unprotected peptides.
• This methodology expands the possibilities for creating complex peptide structures with diverse aromatic modifications.
• The mild reaction conditions, including aqueous compatibility, enhance the practicality of this approach for peptide synthesis.