Post-Assembly Modification of Peptides by Ligand-Enabled β-C(sp<sup>3</sup>)–H Arylation of Alanine at the C-Terminus: Overcoming the Inhibition Effect of Peptide Bonds
Ming Li, Sunday Adewale Akintelu, Bo Yao
Abstract
Postassembly modification of peptides via C(sp3)–H functionalization on aliphatic side chains provides a straightforward approach to access functionalized peptides as therapeutics. However, C(sp3)–H functionalization of C-terminal residues remains underdeveloped due to the inhibition effect of secondary amides in the backbone. Herein, we report a ligand-enabled, bidentate auxiliary-assisted β-C(sp3)–H arylation method, which is well tolerant of secondary amides. A wide range of peptides (tri- to dodecapeptides) underwent position-specific modification of alanine at the C-terminus.
Topics & Concepts
ChemistrySurface modificationAlaninePeptideStereochemistryLigand (biochemistry)Combinatorial chemistryDenticitySide chainAmino acidOrganic chemistryBiochemistryMetalReceptorPhysical chemistryPolymerCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsChemical Synthesis and Analysis