Photoredox Ni-catalyzed Peptide C(sp)-O Cross-coupling: from Intermolecular Reactions to Side Chain-to-tail Macrocyclization

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2019 Jun 12

PMID 31183058

Citations 8

Authors

Hyelee Lee

Nicolas C Boyer

Qiaolin Deng

Hai-Young Kim

Tomi K Sawyer

Nunzio Sciammetta

Affiliations

Soon will be listed here.

Abstract

Ni/photoredox (4DPAIPN) dual catalysis enabled challenging peptide C(sp)-O coupling reactions. Successful cross-coupling reactions were demonstrated with highly functionalized alcohols including side chains of amino acids (, serine, threonine, tyrosine), -4-hydroxy-l-proline, alkyl alcohols, alkynylated alcohols, and carbohydrates. Coupling reactions between bromobenzoyl-capped peptides containing various side chains and either a protected serine building block or a serine-containing dipeptide also proceeded efficiently. Chemoselective C-O coupling (over C-N) was achieved in intermolecular reactions in the presence of a C-terminal primary amide. Furthermore, by judicious structural design in combination with computational modeling, we demonstrated side chain-to-tail macrocyclization of peptides containing a β-turn motif C-O coupling. The methodology developed in this work brings new opportunities for late-stage diversification of complex linear and macrocyclic peptides.

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References

Kubota K, Dai P, Pentelute B, Buchwald S . Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking. J Am Chem Soc. 2018; 140(8):3128-3133. PMC: 5831526. DOI: 10.1021/jacs.8b00172. View

Qvit N, Rubin S, Urban T, Mochly-Rosen D, Gross E . Peptidomimetic therapeutics: scientific approaches and opportunities. Drug Discov Today. 2016; 22(2):454-462. PMC: 5759319. DOI: 10.1016/j.drudis.2016.11.003. View

Vara B, Li X, Berritt S, Walters C, Petersson E, Molander G . Scalable thioarylation of unprotected peptides and biomolecules under Ni/photoredox catalysis. Chem Sci. 2018; 9(2):336-344. PMC: 5868321. DOI: 10.1039/c7sc04292b. View

Halgren T . MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J Comput Chem. 2021; 20(7):730-748. DOI: 10.1002/(SICI)1096-987X(199905)20:7<730::AID-JCC8>3.0.CO;2-T. View

Dougherty P, Qian Z, Pei D . Macrocycles as protein-protein interaction inhibitors. Biochem J. 2017; 474(7):1109-1125. PMC: 6511976. DOI: 10.1042/BCJ20160619. View

Lau J, Dunn M . Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg Med Chem. 2017; 26(10):2700-2707. DOI: 10.1016/j.bmc.2017.06.052. View

Lawson K, Rose T, Harran P . Template-constrained macrocyclic peptides prepared from native, unprotected precursors. Proc Natl Acad Sci U S A. 2013; 110(40):E3753-60. PMC: 3791740. DOI: 10.1073/pnas.1311706110. View

Terrett J, Cuthbertson J, Shurtleff V, MacMillan D . Switching on elusive organometallic mechanisms with photoredox catalysis. Nature. 2015; 524(7565):330-4. PMC: 4545738. DOI: 10.1038/nature14875. View

Uchiro H, Kato R, Arai Y, Hasegawa M, Kobayakawa Y . Total synthesis of hirsutellone B via Ullmann-type direct 13-membered macrocyclization. Org Lett. 2011; 13(23):6268-71. DOI: 10.1021/ol202748e. View

10.

deGruyter J, Malins L, Baran P . Residue-Specific Peptide Modification: A Chemist's Guide. Biochemistry. 2017; 56(30):3863-3873. PMC: 5792174. DOI: 10.1021/acs.biochem.7b00536. View

11.

Chen X, Muthoosamy K, Pfisterer A, Neumann B, Weil T . Site-selective lysine modification of native proteins and peptides via kinetically controlled labeling. Bioconjug Chem. 2012; 23(3):500-8. DOI: 10.1021/bc200556n. View

12.

Yu Y, Zhang L, Buevich A, Li G, Tang H, Vachal P . Chemoselective Peptide Modification via Photocatalytic Tryptophan β-Position Conjugation. J Am Chem Soc. 2018; 140(22):6797-6800. DOI: 10.1021/jacs.8b03973. View

13.

Malins L . Peptide modification and cyclization via transition-metal catalysis. Curr Opin Chem Biol. 2018; 46:25-32. DOI: 10.1016/j.cbpa.2018.03.019. View

14.

Spicer C, Davis B . Selective chemical protein modification. Nat Commun. 2014; 5:4740. DOI: 10.1038/ncomms5740. View

15.

Chen H, Huang R, Li Z, Zhu W, Chen J, Zhan Y . Selective lysine modification of native peptides via aza-Michael addition. Org Biomol Chem. 2017; 15(35):7339-7345. DOI: 10.1039/c7ob01866e. View

16.

Fairlie D, Tyndall J, Reid R, Wong A, Abbenante G, Scanlon M . Conformational selection of inhibitors and substrates by proteolytic enzymes: implications for drug design and polypeptide processing. J Med Chem. 2001; 43(7):1271-81. DOI: 10.1021/jm990315t. View

17.

Ichiishi N, Caldwell J, Lin M, Zhong W, Zhu X, Streckfuss E . Protecting group free radical C-H trifluoromethylation of peptides. Chem Sci. 2018; 9(17):4168-4175. PMC: 5941281. DOI: 10.1039/c8sc00368h. View

18.

Kuethe J, Zhong Y, Yasuda N, Beutner G, Linn K, Kim M . Development of a practical, asymmetric synthesis of the hepatitis C virus protease inhibitor MK-5172. Org Lett. 2013; 15(16):4174-7. DOI: 10.1021/ol401864t. View

19.

Cai Q, Zou B, Ma D . Mild Ullmann-type biaryl ether formation reaction by combination of ortho-substituent and ligand effects. Angew Chem Int Ed Engl. 2006; 45(8):1276-9. DOI: 10.1002/anie.200503538. View

20.

Le C, Wismer M, Shi Z, Zhang R, Conway D, Li G . A General Small-Scale Reactor To Enable Standardization and Acceleration of Photocatalytic Reactions. ACS Cent Sci. 2017; 3(6):647-653. PMC: 5492256. DOI: 10.1021/acscentsci.7b00159. View