Photocatalytic methods for amino acid modification

Abstract

This tutorial review introduces photocatalysis for amino acid modification and summarises recent advances in the field.

Site-selective modification of peptide backbones

“…37 The mechanism is similar to the previous one (conversion 25→28, Scheme 6). 10 Upon irradiation, single electron transfer (SET) took place from the glycine amino group to the pyridinium salt, generating the intermediate 26. The dihydropyridine radical underwent rearomatization, releasing a radical (in the example, R• = Cy•), while the glycyl radical cation underwent H-shift in the presence of base to give a glycyl α-radical (conversion 2627).…”

“…131 Photocatalytic methods also allow selective C-terminal modifications of short peptides, by replacing the carboxyl group by other functions. 10 These reactions are regioselective, due to the difference in reduction/oxidation potentials between the Cterminal carboxyl group and those present in the lateral chains of aspartic and glutamic acid residues. 10,132,133 McMillan et al used this difference in oxidation potentials to carry out a flavincatalyzed decarboxylation of the C-terminus in proteins (Scheme 47, conversion 191→192).…”

“…10 These reactions are regioselective, due to the difference in reduction/oxidation potentials between the Cterminal carboxyl group and those present in the lateral chains of aspartic and glutamic acid residues. 10,132,133 McMillan et al used this difference in oxidation potentials to carry out a flavincatalyzed decarboxylation of the C-terminus in proteins (Scheme 47, conversion 191→192). 133 The resulting α-amino radical underwent a Michael addition to give the final product 192.…”

“…9,10 The advances made in the last years with photoredox reactions are remarkable, since the use of chiral catalysts has allowed the attachment of lateral-chains to the carbon backbone with promising stereoselectivity and good yields. 10 Other strategies such as scission reactions of serine, threonine, hydroxyproline, glutamic acid or C-terminal residues, followed in situ by the addition of new chains, have also been reported, providing from α,β-α,γ-or α,δ-peptide hybrids to peptides with a variety of N-substituents. 11 The oxidation of proline with iron catalysts affords open-chain counterparts.…”

“…These azides can be very useful to expand the chain or ligate peptides using click chemistry. The reader is directed to the review by Spring et al to find other interesting examples of photocatalysis out of the scope of this review 10. …”