Flavin-Mediated Photocatalysis Provides a General Platform for Sulfide C-H Functionalization.

Functionalized sulfides are important in many areas of science, ranging from chemical biology through drug discovery to organic materials chemistry. Sulfides bearing pendant reactive groups in the α-position are particularly useful; however, methods for the selective valorization of simple sulfides or the late-stage functionalization of complex sulfides by the convenient addition of valuable functionality are underexplored. Here we exemplify a general reaction platform for sulfide functionalization by showcasing three modes of α-sulfur C-H functionalization; cyanation, alkenylation, and alkynylation. Using inexpensive and commercially available riboflavin tetraacetate and visible light, decoration of both feedstock and complex sulfides proceeds in a good yield and with high selectivity. Methionine-containing peptides can also be selectively functionalized and a tolerance screen using amino-acid dopants suggests that the platform is compatible with most amino-acid side chains and thus is a potential tool for bioconjugation.

A Vitamin B2 -Photocatalysed Approach to Methionine Analogues.

Access to new non-canonical amino acid residues is crucial for medicinal chemistry and chemical biology. Analogues of the amino acid methionine have been far less explored-despite their use in biochemistry, pharmacology and peptide bioconjugation. This is largely due to limited synthetic access. Herein, we exploit a new disconnection to access non-natural methionines through the development of a photochemical method for the radical α-C-H functionalization of sulfides with alkenes, in water, using inexpensive and commercially-available riboflavin (vitamin B2 ) as a photocatalyst. Our photochemical conditions allow the two-step synthesis of novel methionine analogues-by radical addition to unsaturated amino acid derivatives-and the chemoselective modification of peptide side-chains to yield non-natural methionine residues within small peptides. The mechanism of the bio-inspired flavin photocatalysis has been probed by experimental, DFT and TDDFT studies.

A Vitamin B2-Photocatalysed Approach to Methionine Analogues.

Access to new non-canonical amino acid residues is crucial for medicinal chemistry and chemical biology. Analogues of the amino acid methionine have been far less explored-despite their use in biochemistry, pharmacology and peptide bioconjugation. This is largely due to limited synthetic access. Herein, we exploit a new disconnection to access non-natural methionines through the development of a photochemical method for the radical α-C-H functionalization of sulfides with alkenes, in water, using inexpensive and commercially-available riboflavin (vitamin B2) as a photocatalyst. Our photochemical conditions allow the two-step synthesis of novel methionine analogues-by radical addition to unsaturated amino acid derivatives-and the chemoselective modification of peptide side-chains to yield non-natural methionine residues within small peptides. The mechanism of the bio-inspired flavin photocatalysis has been probed by experimental, DFT and TDDFT studies.