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. 2021 Jan 7;12(7):2467-2473.
doi: 10.1039/d0sc06180h.

Small peptide diversification through photoredox-catalyzed oxidative C-terminal modification

Eliott Le Du  1 , Marion Garreau  1 , Jérôme Waser  1
Affiliations

Small peptide diversification through photoredox-catalyzed oxidative C-terminal modification

Eliott Le Du et al. Chem Sci. .

Abstract

A photoredox-catalyzed oxidative decarboxylative coupling of small peptides is reported, giving access to a variety of N,O-acetals. They were used as intermediates for the addition of phenols and indoles, leading to novel peptide scaffolds and bioconjugates. Amino acids with nucleophilic side chains, such as serine, threonine, tyrosine and tryptophan, could also be used as partners to access tri- and tetrapeptide derivatives with non-natural cross-linking.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. (A) Decarboxylative functionalization of peptides; (B) our photoredox strategy for the synthesis of bioconjugates.
Scheme 2
Scheme 2. Scope of obtained N,O-acetals. Reactions performed on 0.3 mmol scale. Yields of isolated products are given. aCompound obtained with a low diastereoselectivity that could not be determined exactly due to the presence of rotamers.
Scheme 3
Scheme 3. Scope of the one-pot arylation of dipeptides with phenols and indoles. Reactions performed on 0.3 mmol scale. Yields of isolated products are given. aCompound obtained with a low diastereoselectivity that could not be determined exactly due to the presence of rotamers.
Scheme 4
Scheme 4. Preliminary results towards arylation of tetrapeptides. Reactions performed on 1 μmol scale. Relative HPLC ratios of the area of the product over remaining starting material and peptide side-products at 214 nm are given. Average of 3 independent trials. aCalibrated yield, see SI for details. bCompound 8c could not be fully separated from a side product by HPLC.
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