Palladium‐Catalyzed Site‐Selective C(sp²)−H Acetoxylation of Tyrosine‐Containing Peptides

Abstract

A Pd‐catalyzed C(sp2)−H acetoxylation of Tyr‐containing peptides is described. The method relies on the use of a removable 2‐pyridyloxy group as directing group and is distinguished by its reliable scalability and easily tuned regioselectivity to perform mono‐ and diacetoxylation reactions. Remarkably, the assembly of L–DOPA peptidomimetics is beyond reach upon cleavage of the directing group.

Recent developments in the cleavage, functionalization, and conjugation of proteins and peptides at tyrosine residues

“…An extension of the previous work is the Pd-catalyzed ortho -acetoxylation of O -pyridinium protected Tyr peptides. 63 This process was successfully accomplished using Pd(OAc) 2 as the catalyst, and PhI(OAc) 2 as the oxidant in acetonitrile. Changes in the equivalents of oxidant and temperature allowed for the controlled formation of either mono- or diacetoxylated products 35 or 36 ( Fig.…”

Exploring Chemical Modifications of Aromatic Amino Acid Residues in Peptides

“…Removal of the directing group (Py) and subsequent hydrolysis of the acetyl group provided direct access to L-DOPA peptidomimetics with potential applications in medicinal chemistry. 60c…”

Research progress on chemical modifications of tyrosine residues in peptides and proteins

“…The group of Correa developed a palladium‐catalyzed pyridine‐directed acetoxylation of Tyr residues (Scheme 23c) (Urruzuno et al, 2023). Pyridine was selected as the directing group for the acetylation of peptides containing Tyr residues.…”