N‐Methylation of Twenty Different α‐Amino Acid Motifs Using Methanol under Metal‐Loaded Titanium Dioxide Photocatalysis

Abstract

AbstractEfficient N‐methylation is highly required for the synthesis of N‐methylated α‐amino acids and peptides, both of which are essential motifs in biochemical applications. Herein, we report a photocatalytic system using metal‐loaded titanium dioxide in methanol under near‐UV light irradiation for N‐methylation of α‐amino acid or its derivatives at ambient temperature without wasteful stoichiometric reagents. The present method enables the N‐methylation of twenty kinds of α‐amino acid motifs found in proteins in the human body, whether polar/non‐polar or acidic/basic functional groups are embedded in the substrates. Dipeptides also undergo the N‐methylation at the N‐terminal while the peptide bond and carboxylic acid remain intact. Most of the N‐methylated products can be isolated through simple filtration and concentration without tedious purification processes such as an aqueous workup and column chromatography.