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. 2020 Nov 25;142(47):20143-20151.
doi: 10.1021/jacs.0c09678. Epub 2020 Oct 30.

Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light

Rajdip Chowdhury  1 , Zhunzhun Yu  1 , My Linh Tong  1 , Stefanie V Kohlhepp  1 , Xiang Yin  1 , Abraham Mendoza  1
Affiliations

Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light

Rajdip Chowdhury et al. J Am Chem Soc. .

Abstract

Photoexcited dihydronicotinamides like NADH and analogues have been found to generate alkyl radicals upon reductive decarboxylation of redox-active esters without auxiliary photocatalysts. This principle allowed aliphatic photocoupling between redox-active carboxylate derivatives and electron-poor olefins, displaying surprising water and air-tolerance and unusually high coupling rates in dilute conditions. The orthogonality of the reaction in the presence of other carboxylic acids and its utility in the functionalization of DNA is presented, notably using visible light in combination with NADH, the ubiquitous reductant of life.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Approach Towards Aliphatic Photo-Coupling with Native NADH Bio-Photoreductant
NAD, Nicotinamide Adenine Dinucleotide; PET, Photoinduced Electron Transfer; 5 – R = Ph, R’= H.
Scheme 2
Scheme 2. Discovery of the Photo-Coupling Promoted by BuNAH (10) and NADH (11)
Determined by 1H NMR using 1,1,2,2- tetrachloroethane as internal standard. 3 equiv used. 10 equiv used.
Scheme 3
Scheme 3. Scope Study
Yields were determined by 1H NMR using an appropriate internal standard; for isolated yields at preparative concentrations, see SI. HE; Hantzsch ester (9). Ar atmosphere. 100 mM concentration. DMSO was used as solvent. Dihydropyridine 9 was used instead of BuNAH (10) for comparison. 20 mM concentration.
Scheme 4
Scheme 4. Alkyl Photo-Coupling on DNA
Reaction time 2 h. Reaction time 4 h. Buffer pH 5.5. Coupling product was detected by MS but could not be quantified due to insufficient chromatographic resolution. ND, Not Determined.
Scheme 5
Scheme 5. Kinetic Profiling of the Photo-Coupling by No-D 1H NMR
Scheme 6
Scheme 6. Mechanistic Studies
Scheme 7
Scheme 7. Proposed Mechanism
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References

    1. Ankenbruck N.; Courtney T.; Naro Y.; Deiters A. Optochemical Control of Biological Processes in Cells and Animals. Angew. Chem., Int. Ed. 2018, 57 (11), 2768–2798. 10.1002/anie.201700171. - DOI - PMC - PubMed
    2. Fehrentz T.; Schönberger M.; Trauner D. Optochemical Genetics. Angew. Chem., Int. Ed. 2011, 50 (51), 12156–12182. 10.1002/anie.201103236. - DOI - PubMed
    3. Albert L.; Vázquez O. Photoswitchable Peptides for Spatiotemporal Control of Biological Functions. Chem. Commun. 2019, 55 (69), 10192–10213. 10.1039/C9CC03346G. - DOI - PubMed
    4. Szymański W.; Beierle J. M.; Kistemaker H. A. V.; Velema W. A.; Feringa B. L. Reversible Photocontrol of Biological Systems by the Incorporation of Molecular Photoswitches. Chem. Rev. 2013, 113 (8), 6114–6178. 10.1021/cr300179f. - DOI - PubMed
    5. Heinrich B.; Bouazoune K.; Wojcik M.; Bakowsky U.; Vázquez O. ortho-Fluoroazobenzene Derivatives as DNA Intercalators for Photocontrol of DNA and Nucleosome Binding by Visible Light. Org. Biomol. Chem. 2019, 17 (7), 1827–1833. 10.1039/C8OB02343C. - DOI - PubMed
    6. Broichhagen J.; Trauner D. The in vivo Chemistry of Photoswitched Tethered Ligands. Curr. Opin. Chem. Biol. 2014, 21, 121–127. 10.1016/j.cbpa.2014.07.008. - DOI - PubMed
    1. Klán P.; Šolomek T.; Bochet C. G.; Blanc A.; Givens R.; Rubina M.; Popik V.; Kostikov A.; Wirz J. Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy. Chem. Rev. 2013, 113 (1), 119–191. 10.1021/cr300177k. - DOI - PMC - PubMed
    2. Kolarski D.; Sugiyama A.; Breton G.; Rakers C.; Ono D.; Schulte A.; Tama F.; Itami K.; Szymanski W.; Hirota T.; Feringa B. L. Controlling the Circadian Clock with High Temporal Resolution through Photodosing. J. Am. Chem. Soc. 2019, 141 (40), 15784–15791. 10.1021/jacs.9b05445. - DOI - PMC - PubMed
    1. Devaraj N. K. The Future of Bioorthogonal Chemistry. ACS Cent. Sci. 2018, 4 (8), 952–959. 10.1021/acscentsci.8b00251. - DOI - PMC - PubMed

    1. For examples of nonlight regulated bioorthogonal reactions, see:

    2. Sletten E. M.; Bertozzi C. R. Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality. Angew. Chem., Int. Ed. 2009, 48 (38), 6974–6998. 10.1002/anie.200900942. - DOI - PMC - PubMed
    3. Patterson D. M.; Nazarova L. A.; Prescher J. A. Finding the Right (Bioorthogonal) Chemistry. ACS Chem. Biol. 2014, 9 (3), 592–605. 10.1021/cb400828a. - DOI - PubMed
    4. Whiting M.; Muldoon J.; Lin Y.-C.; Silverman S. M.; Lindstrom W.; Olson A. J.; Kolb H. C.; Finn M. G.; Sharpless K. B.; Elder J. H.; Fokin V. V. Inhibitors of HIV-1 Protease by Using In Situ Click Chemistry. Angew. Chem., Int. Ed. 2006, 45 (9), 1435–1439. 10.1002/anie.200502161. - DOI - PubMed
    5. Fang Y.; Zhang H.; Huang Z.; Scinto S. L.; Yang J. C.; Am Ende C. W.; Dmitrenko O.; Johnson D. S.; Fox J. M. Photochemical Syntheses, Transformations, and Bioorthogonal Chemistry of Trans-Cycloheptene and Sila Trans-Cycloheptene Ag(I) complexes. Chem. Sci. 2018, 9 (7), 1953–1963. 10.1039/C7SC04773H. - DOI - PMC - PubMed
    6. An P.; Lewandowski T. M.; Erbay T. G.; Liu P.; Lin Q. Sterically Shielded, Stabilized Nitrile Imine for Rapid Bioorthogonal Protein Labeling in Live Cells. J. Am. Chem. Soc. 2018, 140 (14), 4860–4868. 10.1021/jacs.8b00126. - DOI - PMC - PubMed
    7. Blackman M. L.; Royzen M.; Fox J. M. Tetrazine Ligation: Fast Bioconjugation Based on Inverse-Electron-Demand Diels–Alder Reactivity. J. Am. Chem. Soc. 2008, 130 (41), 13518–13519. 10.1021/ja8053805. - DOI - PMC - PubMed
    8. Patterson D. M.; Nazarova L. A.; Xie B.; Kamber D. N.; Prescher J. A. Functionalized Cyclopropenes As Bioorthogonal Chemical Reporters. J. Am. Chem. Soc. 2012, 134 (45), 18638–18643. 10.1021/ja3060436. - DOI - PubMed
    9. Sachdeva A.; Wang K.; Elliott T.; Chin J. W. Concerted, Rapid, Quantitative, and Site-Specific Dual Labeling of Proteins. J. Am. Chem. Soc. 2014, 136 (22), 7785–7788. 10.1021/ja4129789. - DOI - PMC - PubMed
    10. Laughlin S. T.; Baskin J. M.; Amacher S. L.; Bertozzi C. R. In Vivo Imaging of Membrane-Associated Glycans in Developing Zebrafish. Science 2008, 320 (5876), 664–667. 10.1126/science.1155106. - DOI - PMC - PubMed

    1. For examples of light-regulated bioorthogonal reactions:

    2. Tasdelen M. A.; Yagci Y. Light-Induced Click Reactions. Angew. Chem., Int. Ed. 2013, 52 (23), 5930–5938. 10.1002/anie.201208741. - DOI - PubMed
    3. Chen R. T.; Marchesan S.; Evans R. A.; Styan K. E.; Such G. K.; Postma A.; McLean K. M.; Muir B. W.; Caruso F. Photoinitiated Alkyne–Azide Click and Radical Cross-Linking Reactions for the Patterning of PEG Hydrogels. Biomacromolecules 2012, 13 (3), 889–895. 10.1021/bm201802w. - DOI - PubMed
    4. Singh K.; Fennell C. J.; Coutsias E. A.; Latifi R.; Hartson S.; Weaver J. D. Light Harvesting for Rapid and Selective Reactions: Click Chemistry with Strain-Loadable Alkenes. Chem. 2018, 4 (1), 124–137. 10.1016/j.chempr.2017.11.007. - DOI
    5. Kaur G.; Singh G.; Singh J. Photochemical Tuning of Materials: A Click Chemistry Perspective. Mater. Today Chem. 2018, 8, 56–84. 10.1016/j.mtchem.2018.03.002. - DOI
    6. Bordoni A. V.; Lombardo M. V.; Wolosiuk A. Photochemical radical thiol–ene click-based methodologies for silica and transition metal oxides materials chemical modification: a mini-review. RSC Adv. 2016, 6 (81), 77410–77426. 10.1039/C6RA10388J. - DOI
    7. Ramil C. P.; Lin Q. Photoclick chemistry: a fluorogenic light-triggered in vivo ligation reaction. Curr. Opin. Chem. Biol. 2014, 21, 89–95. 10.1016/j.cbpa.2014.05.024. - DOI - PMC - PubMed

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