Solar and Visible Light Assisted Peptide Coupling.

ABSTRACT

Amino acid and peptide couplings are widely used in fields related to pharma and materials. Still, current peptide synthesis continues to rely on the use of expensive, water sensitive, and waste-generating coupling reagents, which are often prepared in multi-step sequences and used in excess. Herein is described a peptide coupling reaction design that relies mechanistically on sun-light activation of a 4-dimethylamino-pyridine-alkyl halide charge-transfer complex to generate a novel coupling reagent in situ. The resulting coupling method is rapid, does not require dry solvents or inert atmosphere, and is compatible with all the most common amino acids and protecting groups. Peptide couplings can be run on gram-scale, without the use of special equipment. This method has a significantly reduced environmental and financial footprint compared to standard peptide coupling reactions. Experimental and computational studies support the proposed mechanism.