Selective N-Arylation of p-Aminophenylalanine in Unprotected Peptides with Organometallic Palladium Reagents.

ABSTRACT: The selective N-arylation of p-aminophenylalanine in polypeptides with pre-formed palladium oxidative addition complexes is described. The depressed pKa of the aniline NH₂ group enables chemoselective C-N bond formation on peptides containing multiple other aliphatic amino groups at lysines or the N-terminus via Curtin-Hammett control under mild conditions. Using palladium complexes derived from electron-poor aryl halides, p-aminophenylalanine is fully arylated in aqueous buffer in as little as one hour at micromolar concentrations. A complementary protocol using the non-nucleophilic, organic base 1,5-diazabicyclo(4.3.0)non-5-ene (DBN), expands the substrate scope to tolerate electron-rich functional groups provides up to 97 % conversion. These procedures enable the chemoselecti

SUBMITTER: Mallek AJ 

PROVIDER: S-EPMC12822359 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature