Pyridoxal-Inspired Photo-Decarboxylase Catalysis: Photochemical Decarboxylation of Unprotected Amino Acids

Abstract

A photochemical organocatalytic method for the protodecarboxylation of unprotected amino acids is reported. Inspired by pyridoxal 5′-phosphate-dependent decarboxylase enzymes, the catalytic activation of amino acid substrates by 3-hydroxyisonicotinaldehyde enables a photochemical decarboxylation event, which can be leveraged in combination with a thiol co-catalyst. The necessary and sufficient structural features of the pyridoxal-like framework for photoactivity are determined using ultraviolet-visible absorption spectroscopy. A broad scope of unprotected amino acids can be decarboxylated in this system, with selectivity between multiple carboxylates realized on the possible basis of hyperconjugation. The ability to engage simple amino acids in decarboxylative functionalization at ambient conditions using a pyridoxal-mimicking organocatalyst enables new possibilities for the translation of biogenic amino acids into medicinally valuable amines.