Skeletal remodeling of inert amides using N-trideuteromethyl anthranilium salts

Reprogramming the amino acid building blocks in biomolecules has emerged as an efficient tool to quickly expand the multifaceted space and build additional biocapabilities, particularly via precise editing of peptide bonds in genetic code expansion. Here, we implement a synthetic version that employs anthranilium triflates, which are preinstalled with trideuterium-labeled methyl groups, as multi-functional non-natural aromatic cyclic β 2,3 -amino acid synthons to construct versatile site-specific N-CD 3 oligoamides and peptides through direct incorporation of the anthranilyl unit into various inert amides. This functional insertion strategy diversifies a wide range of pharmaceuticals, natural products, and bioactive molecules, which enables access to diverse oligoamide-containing molecules and results in synthetically challenging analog with promising potencies.