Photoredox C(2)-Arylation of Indole- and Tryptophan-Containing Biomolecules

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2024 May 2

PMID 38696591

Authors

Bruno M da S Santos

Fernanda G Finelli

David R Spring

Affiliations

Soon will be listed here.

Abstract

We introduce a novel and straightforward methodology for photoredox arylation of an indole scaffold using aryldiazonium salts under mild and metal-free conditions. Our approach enables the regioselective and chemoselective introduction of several aryl groups to the C(2) position of indoles and tryptophan, even in competition with other amino acids. This approach extends to the late-stage functionalization of peptides and lysozyme, heralding the unprecedented arylation of tryptophan residues in wild-type proteins and offering broad utility in chemical biology.

References

Reay A, Hammarback L, Bray J, Sheridan T, Turnbull D, Whitwood A . Mild and Regioselective Pd(OAc)-Catalyzed C-H Arylation of Tryptophans by [ArN]X, Promoted by Tosic Acid. ACS Catal. 2017; 7(8):5174-5179. PMC: 5557615. DOI: 10.1021/acscatal.6b03121. View

Gilis D, Massar S, Cerf N, Rooman M . Optimality of the genetic code with respect to protein stability and amino-acid frequencies. Genome Biol. 2001; 2(11):RESEARCH0049. PMC: 60310. DOI: 10.1186/gb-2001-2-11-research0049. View

Bellotti P, Huang H, Faber T, Glorius F . Photocatalytic Late-Stage C-H Functionalization. Chem Rev. 2023; 123(8):4237-4352. DOI: 10.1021/acs.chemrev.2c00478. View

Vinogradova E, Zhang C, Spokoyny A, Pentelute B, Buchwald S . Organometallic palladium reagents for cysteine bioconjugation. Nature. 2015; 526(7575):687-91. PMC: 4809359. DOI: 10.1038/nature15739. View

Mupparapu N, Brewster L, Ostrom K, Elshahawi S . Late-Stage Chemoenzymatic Installation of Hydroxy-Bearing Allyl Moiety on the Indole Ring of Tryptophan-Containing Peptides. Chemistry. 2022; 28(20):e202104614. PMC: 9314954. DOI: 10.1002/chem.202104614. View

Bradley S, Lehka B, Hansson F, Adhikari K, Rago D, Rubaszka P . Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast. Nat Chem Biol. 2023; 19(12):1551-1560. PMC: 10667104. DOI: 10.1038/s41589-023-01430-2. View

Li Y, Vaz R, Olson S, Munson M, Paras N, Conrad J . Selectivity in the Addition of Electron Deficient Radicals to the 2 Position of Indoles. European J Org Chem. 2021; 2020(36):5828-5832. PMC: 7939109. DOI: 10.1002/ejoc.201901784. View

Yi W, Xiao P, Liu X, Zhao Z, Sun X, Wang J . Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry. Signal Transduct Target Ther. 2022; 7(1):386. PMC: 9716178. DOI: 10.1038/s41392-022-01250-1. View

Kufleitner M, Haiber L, Wittmann V . Metabolic glycoengineering - exploring glycosylation with bioorthogonal chemistry. Chem Soc Rev. 2022; 52(2):510-535. DOI: 10.1039/d2cs00764a. View

10.

Lima R, Delgado J, Bernardi D, Berlinck R, Kaplaneris N, Ackermann L . Post-synthetic functionalization of tryptophan protected peptide sequences through indole (C-2) photocatalytic alkylation. Chem Commun (Camb). 2021; 57(47):5758-5761. DOI: 10.1039/d1cc01822a. View

11.

Krajcovicova S, Spring D . Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation. Angew Chem Int Ed Engl. 2023; 62(34):e202307782. DOI: 10.1002/anie.202307782. View

12.

Mao M, Li J, Dong K, Li R, Chen X, Liu J . Metal-Free Late-Stage Alkylation of Tryptophan and Tryptophan-Containing Peptides with 1,3-Dithiane Derivatives. Org Lett. 2023; 25(31):5784-5789. DOI: 10.1021/acs.orglett.3c02033. View

13.

Li B, Kim D, Bloom S, Huang R, Qiao J, Ewing W . Site-selective tyrosine bioconjugation via photoredox catalysis for native-to-bioorthogonal protein transformation. Nat Chem. 2021; 13(9):902-908. DOI: 10.1038/s41557-021-00733-y. View

14.

Naveen N, Sengupta S, Chandrasekaran S . Metal-Free S-Arylation of Cysteine Using Arenediazonium Salts. J Org Chem. 2018; 83(7):3562-3569. DOI: 10.1021/acs.joc.7b03160. View

15.

Bottecchia C, Noel T . Photocatalytic Modification of Amino Acids, Peptides, and Proteins. Chemistry. 2018; 25(1):26-42. PMC: 6348373. DOI: 10.1002/chem.201803074. View

16.

Rahimidashaghoul K, Klimankova I, Hubalek M, Korecky M, Chvojka M, Pokorny D . Reductant-Induced Free Radical Fluoroalkylation of Nitrogen Heterocycles and Innate Aromatic Amino Acid Residues in Peptides and Proteins. Chemistry. 2019; 25(69):15779-15785. DOI: 10.1002/chem.201902944. View

17.

Lee J, Cuthbertson J, Mitchell N . Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan. Org Lett. 2023; 25(29):5459-5464. PMC: 10391624. DOI: 10.1021/acs.orglett.3c01795. View

18.

Docherty J, Lister T, McArthur G, Findlay M, Domingo-Legarda P, Kenyon J . Transition-Metal-Catalyzed C-H Bond Activation for the Formation of C-C Bonds in Complex Molecules. Chem Rev. 2023; 123(12):7692-7760. PMC: 10311463. DOI: 10.1021/acs.chemrev.2c00888. View

19.

Bottecchia C, Rubens M, Gunnoo S, Hessel V, Madder A, Noel T . Visible-Light-Mediated Selective Arylation of Cysteine in Batch and Flow. Angew Chem Int Ed Engl. 2017; 56(41):12702-12707. PMC: 5656832. DOI: 10.1002/anie.201706700. View

20.

Kaplaneris N, Puet A, Kallert F, Pohlmann J, Ackermann L . Late-stage C-H Functionalization of Tryptophan-Containing Peptides with Thianthrenium Salts: Conjugation and Ligation. Angew Chem Int Ed Engl. 2022; 62(9):e202216661. DOI: 10.1002/anie.202216661. View