On-Resin Photochemical Decarboxylative Arylation of Peptides

Abstract

Here we describe the application of photochemical decarboxylative arylation as a late-stage functionalization reaction for peptides. The reaction uses redox-active esters of aspartic acid and glutamic acid on the solid phase to provide analogues of aromatic amino acids. By using aryl bromides as arylation reagents, a wide variety of amino acids can be accessed without having to synthesize them individually in solution. The reaction is compatible with proteinogenic amino acids and was used to perform a structure–activity relationship study of a PRMT5 binding peptide.

Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes

“…Moreover, on-resin modification brings forth substantial practical advantages, addressing key challenges related to purification and solubility that are often encountered in peptide chemistry in solution. Specifically, considering the well-documented compatibility of redox-active ester synthesis with solid-phase approaches 47 , 59 , 60 , and the mild basic condition of our two-step protocol, we hypothesized that adapting this photochemical transformation to heterogeneous conditions on resin would be an attainable objective.…”

Metal-free Photocatalytic Cross-Electrophile Coupling enables C1 Homologation and Alkylation of Carboxylic Acids with Aldehydes

“…[58,59] Moreover, on-resin modification brings forth substantial practical advantages, addressing key challenges related to purification and solubility that are often encountered in peptide chemistry in solution. Specifically, considering the well-documented compatibility of redox-active ester synthesis with solid-phase approaches, [49,60,61] and the mild basic condition of our two-step protocol, we hypothesized that adapting this photochemical transformation to heterogeneous conditions on resin would be an attainable objective.…”