Olefin-Catalyzed Aromatic Bromination toward Biocompatible Tyrosine Modification

Area of Science:

• Chemical Biology
• Organic Chemistry
• Biomolecular Engineering

Background:

• Chemical modification of biomolecules is key to understanding biological processes.
• Catalysis offers advantages in selectivity and control over stoichiometric methods.
• Tyrosine modification is significant due to its biological roles, but selective bromination is challenging under physiological conditions.

Purpose of the Study:

• To develop a catalyst-controlled aromatic bromination method under near-physiological conditions.
• To enable efficient and selective tyrosine bromination for biomolecular labeling.
• To create a light-activated catalytic system for in situ modification.

Main Methods:

• Developed catalytic aromatic bromination using in-situ generated bromiranium ions from cyclic olefins.
• Employed bifunctional cyclooctenes with a hydroxybenzyl group as catalysts.
• Investigated substituent effects on catalyst generation rates and kinetics.
• Demonstrated light-gated catalysis via photochemical deprotection.

Main Results:

• Efficient bromination of phenol derivatives and tyrosine residues was achieved.
• Catalysis was compatible with aqueous conditions, enabling peptide modification.
• Light-activated catalysis allowed for spatiotemporal control of bromination.
• The method demonstrated Lewis-base catalysis even under acidic conditions.

Conclusions:

• Developed a novel olefin-based catalytic system for aromatic bromination.
• The method provides a biocompatible and efficient approach for tyrosine modification.
• The light-gated capability offers precise control for in situ biomolecular labeling.