C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation

Garreau, Marion; Vaillant, Franck Le; Waser, Jérôme

doi:10.1002/anie.201901922

Cited by 117 publications

(82 citation statements)

References 86 publications

(35 reference statements)

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“…The chloromethyl radical generation by photoredox catalysis is a useful strategy for cyclopropanation [58]. Most photoredox catalyzed, decarboxylative generations of carbon-centered radicals are based on the formation of "stabilized" α-amino [59][60][61][62][63][64][65] or benzyl [66][67][68][69][70] radical species. However, the generation of unstabilized alkyl radical species is also known [71][72][73][74].…”

Section: Resultsmentioning

confidence: 99%

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Vliet¹,

Leeuwen²,

Brouwer³

et al. 2020

Beilstein J. Org. Chem.

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Where monochloroacetic acid is widely used as a starting material for the synthesis of relevant groups of compounds, many of these synthetic procedures are based on nucleophilic substitution of the carbon chlorine bond. Oxidative or reductive activation of monochloroacetic acid results in radical intermediates, leading to reactivity different from the traditional reactivity of this compound. Here, we investigated the possibility of applying monochloroacetic acid as a substrate for photoredox catalysis with styrene to directly produce γ-phenyl-γ-butyrolactone. Instead of using nucleophilic substitution, we cleaved the carbon chlorine bond by single-electron reduction, creating a radical species. We observed that the reaction works best in nonpolar solvents. The reaction does not go to full conversion, but selectively forms γ-phenyl-γ-butyrolactone and 4-chloro-4-phenylbutanoic acid. Over time the catalyst precipitates from solution (perhaps in a decomposed form in case of fac-[Ir(ppy)3]), which was proven by mass spectrometry and EPR spectroscopy for one of the catalysts (N,N-5,10-di(2-naphthalene)-5,10-dihydrophenazine) used in this work. The generation of HCl resulting from lactone formation could be an additional problem for organometallic photoredox catalysts used in this reaction. In an attempt to trap one of the radical intermediates with TEMPO, we observed a compound indicating the generation of a chloromethyl radical.

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Section: Resultsmentioning

confidence: 99%

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Vliet¹,

Leeuwen²,

Brouwer³

et al. 2020

Beilstein J. Org. Chem.

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“…[7] Through photoredox catalysis, selective C-terminal functionalization has been achieved due to the difference in oxidation potential relative to side-chain residues (Scheme 1 c). [8] Esterification of carboxylic acids is a well-established prodrug strategy and recently Raines et al demonstrated how esterification with diazo compounds can enable the translocation of a putative therapeutic agent across the plasma membrane (Scheme 1 d). [9] Peptides and proteins are already highly complex molecules with several stereocenters, and adding additional complexity through a stereoselective bioconjugation strategy could lead to higher selectivity towards the chiral environment present in receptors.…”

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confidence: 99%

Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes

et al. 2020

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The first stereoselective, near-equimolar, and metalfree oxidative bioconjugation of amino acids and oligopeptides to aldehydes is presented. Based on a newly developed organocatalytic oxidative concept, the C-terminal and sidechain carboxylic acid functionalities of amino acids and oligopeptides are shown to couple in a stereoselective manner to a-branched aldehydes catalyzed by a chiral primary amine and a quinone as oxidizing agent. The oxidative coupling generally proceeds in high yield. For aspartic acid, selective coupling of the side-chain, or the C-terminal carboxylic acid, is demonstrated depending on the protection strategy. The stereoselective, oxidative bioconjugation concept is extended to a series of oligopeptides where coupling to carboxylic acid functionalities is presented. Bioorthogonal linker molecules for further functionalization are obtained by merging the oxidative coupling strategy with the click concept. It is demonstrated that the configuration of the new stereocenter is determined exclusively by the organocatalyst.

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“…[19] Zeitler and coworkers later showed that the reported conditions led to the incorporation of only three diphenylamine units. [23] Substitution with electron-withdrawing groups led to 4ClDPAIPN (3b)a nd 4BrDPAIPN (3c). [23] Substitution with electron-withdrawing groups led to 4ClDPAIPN (3b)a nd 4BrDPAIPN (3c).…”

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confidence: 99%

“…Using TIPS-EBX (1a,T IPS = triisopropylsilyl) and Ir catalyst 4 led to decomposition of the reagent, which was faster than the desired alkynylation. [23] For 2c,w eo bserved full consumption of the catalyst, indicating stability issues. [10j, 24] Thestronger oxidant 4ClCzIPN (2b) afforded 89 %y ield.…”

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confidence: 99%

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C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation

2019

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We report the first decarboxylative alkynylation of the C-terminus of peptides starting from free carboxylicacids. The reaction is fast, metal-free,and proceeds cleanly to afford alkynylated peptides with abroad tolerance for the C-terminal amino acid. By the use of hypervalent iodine reagents,t he introduction of ab road range of functional groups was successful. C-terminal selectivity was achieved by differentiation of the oxidation potentials of the carboxylic acids based on the use of fine-tuned organic dyes.Scheme 1. Photoredox-catalyzed decarboxylation strategies for the functionalization of peptides. EWG = Electron-withdrawing group, Phth = phthaloyl, FG = functionalg roup.

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C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation

Cited by 117 publications

References 86 publications

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes

C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation

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