Photoenzymatic catalysis has become an emerging field in organic synthetic chemistry that provides eco-friendly alternatives to traditional methods. This comprehensive review examines the developing field of photoenzymatic catalysis, categorized by reaction types and focusing on its application in organic synthesis. This article highlights recent advances in the use of photoenzymatic reactions in carbon-carbon cross-coupling, ketone and alkene reduction, hydroamination, and hydrosulfonylation, mostly by flavin-dependent “ene”-reductases and nitroreductases. In each case, we exemplified the substrate scope that produces products with high yield and enantioselectivity. Additionally, the emerging trends in developing new enzymatic variants and novel reaction pathways that broaden the scope and enhance yield of these reactions were discussed.
References
[1]
Candish, L., Collins, K.D., Cook, G.C., Douglas, J.J., Gómez-Suárez, A., Jolit, A., et al. (2021) Photocatalysis in the Life Science Industry. Chemical Reviews, 122, 2907-2980. https://doi.org/10.1021/acs.chemrev.1c00416
[2]
Xu, J., Hu, Y., Fan, J., Arkin, M., Li, D., Peng, Y., et al. (2019) Light‐Driven Kinetic Resolution of α‐Functionalized Carboxylic Acids Enabled by an Engineered Fatty Acid Photodecarboxylase. Angewandte Chemie International Edition, 58, 8474-8478. https://doi.org/10.1002/anie.201903165
[3]
Santner, P., Szabó, L.K., Chanquia, S.N., Merrild, A.H., Hollmann, F., Kara, S., et al. (2021) Optimization and Engineering of Fatty Acid Photodecarboxylase for Substrate Specificity. ChemCatChem, 13, 4038-4046. https://doi.org/10.1002/cctc.202100840
[4]
Dhakshinamoorthy, A., Asiri, A.M. and Garcia, H. (2020) Catalysis in Confined Spaces of Metal Organic Frameworks. ChemCatChem, 12, 4732-4753. https://doi.org/10.1002/cctc.202001188
[5]
Ji, P., Feng, X., Oliveres, P., Li, Z., Murakami, A., Wang, C., et al. (2019) Strongly Lewis Acidic Metal-Organic Frameworks for Continuous Flow Catalysis. Journal of the American Chemical Society, 141, 14878-14888. https://doi.org/10.1021/jacs.9b07891
[6]
Shultz, C.S. and Krska, S.W. (2007) Unlocking the Potential of Asymmetric Hydrogenation at Merck. Accounts of Chemical Research, 40, 1320-326. https://doi.org/10.1021/ar700141v
[7]
Lucas, E.L. and Jarvo, E.R. (2017) Stereospecific and Stereoconvergent Cross-Couplings between Alkyl Electrophiles. Nature Reviews Chemistry, 1, Article No. 0065. https://doi.org/10.1038/s41570-017-0065
[8]
Li, M., Harrison, W., Zhang, Z., Yuan, Y. and Zhao, H. (2023) Remote Stereocontrol with Azaarenes via Enzymatic Hydrogen Atom Transfer. Nature Chemistry, 16, 277-284. https://doi.org/10.1038/s41557-023-01368-x
[9]
Huang, X., Wang, B., Wang, Y., Jiang, G., Feng, J. and Zhao, H. (2020) Photoenzymatic Enantioselective Intermolecular Radical Hydroalkylation. Nature, 584, 69-74. https://doi.org/10.1038/s41586-020-2406-6
[10]
Huang, X., Feng, J., Cui, J., Jiang, G., Harrison, W., Zang, X., et al. (2022) Photoinduced Chemomimetic Biocatalysis for Enantioselective Intermolecular Radical Conjugate Addition. Nature Catalysis, 5, 586-593. https://doi.org/10.1038/s41929-022-00777-4
[11]
Sun, S., Nicholls, B.T., Bain, D., Qiao, T., Page, C.G., Musser, A.J., et al. (2023) Enantioselective Decarboxylative Alkylation Using Synergistic Photoenzymatic Catalysis. Nature Catalysis, 7, 35-42. https://doi.org/10.1038/s41929-023-01065-5
[12]
Bender, S.G. and Hyster, T.K. (2023) Pyridylmethyl Radicals for Enantioselective Alkene Hydroalkylation Using “Ene”-Reductases. ACS Catalysis, 13, 14680-14684. https://doi.org/10.1021/acscatal.3c03771
[13]
Ouyang, Y., Turek-Herman, J., Qiao, T. and Hyster, T.K. (2023) Asymmetric Carbohydroxylation of Alkenes Using Photoenzymatic Catalysis. Journal of the American Chemical Society, 145, 17018-17022. https://doi.org/10.1021/jacs.3c06618
[14]
Zhao, B., Feng, J., Yu, L., Xing, Z., Chen, B., Liu, A., et al. (2023) Direct Visible-Light-Excited Flavoproteins for Redox-Neutral Asymmetric Radical Hydroarylation. Nature Catalysis, 6, 996-1004. https://doi.org/10.1038/s41929-023-01024-0
Page, C.G., Cao, J., Oblinsky, D.G., MacMillan, S.N., Dahagam, S., Lloyd, R.M., et al. (2023) Regioselective Radical Alkylation of Arenes Using Evolved Photoenzymes. Journal of the American Chemical Society, 145, 11866-11874. https://doi.org/10.1021/jacs.3c03607
[17]
Fu, H., Qiao, T., Carceller, J.M., MacMillan, S.N. and Hyster, T.K. (2023) Asymmetric C-Alkylation of Nitroalkanes via Enzymatic Photoredox Catalysis. Journal of the American Chemical Society, 145, 787-793. https://doi.org/10.1021/jacs.2c12197
[18]
Fu, H., Cao, J., Qiao, T., Qi, Y., Charnock, S.J., Garfinkle, S., et al. (2022) An Asymmetric sp3-sp3 Cross-Electrophile Coupling Using ‘Ene’-Reductases. Nature, 610, 302-307. https://doi.org/10.1038/s41586-022-05167-1
Biegasiewicz, K.F., Cooper, S.J., Gao, X., Oblinsky, D.G., Kim, J.H., Garfinkle, S.E., et al. (2019) Photoexcitation of Flavoenzymes Enables a Stereoselective Radical Cyclization. Science, 364, 1166-1169. https://doi.org/10.1126/science.aaw1143
[21]
Clayman, P.D. and Hyster, T.K. (2020) Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization. Journal of the American Chemical Society, 142, 15673-15677. https://doi.org/10.1021/jacs.0c07918
[22]
Zhu, C., Yuan, Z., Deng, Z., Yin, D., Zhang, Y., Zhou, J., et al. (2023) Photoenzymatic Enantioselective Synthesis of Oxygen‐Containing Benzo‐Fused Heterocycles. Angewandte Chemie International Edition, 62, e202311762. https://doi.org/10.1002/anie.202311762
[23]
Prats Luján, A., Bhat, M.F., Saravanan, T. and Poelarends, G.J. (2022) Chemo‐ and Enantioselective Photoenzymatic Ketone Reductions Using a Promiscuous Flavin‐Dependent Nitroreductase. ChemCatChem, 14, e202200043. https://doi.org/10.1002/cctc.202200043
[24]
Sandoval, B.A., Kurtoic, S.I., Chung, M.M., Biegasiewicz, K.F. and Hyster, T.K. (2019) Photoenzymatic Catalysis Enables Radical‐Mediated Ketone Reduction in Ene‐Reductases. Angewandte Chemie International Edition, 58, 8714-8718. https://doi.org/10.1002/anie.201902005
[25]
Nakano, Y., Black, M.J., Meichan, A.J., Sandoval, B.A., Chung, M.M., Biegasiewicz, K.F., et al. (2020) Photoenzymatic Hydrogenation of Heteroaromatic Olefins Using ‘Ene’‐Reductases with Photoredox Catalysts. Angewandte Chemie International Edition, 59, 10484-10488. https://doi.org/10.1002/anie.202003125
[26]
Sandoval, B.A., Clayman, P.D., Oblinsky, D.G., Oh, S., Nakano, Y., Bird, M., et al. (2020) Photoenzymatic Reductions Enabled by Direct Excitation of Flavin-Dependent “Ene”-Reductases. Journal of the American Chemical Society, 143, 1735-1739. https://doi.org/10.1021/jacs.0c11494
[27]
Luján, A.P., Bhat, M.F., Tsaturyan, S., van Merkerk, R., Fu, H. and Poelarends, G.J. (2023) Tailored Photoenzymatic Systems for Selective Reduction of Aliphatic and Aromatic Nitro Compounds Fueled by Light. Nature Communications, 14, Article No. 5442. https://doi.org/10.1038/s41467-023-41194-w
[28]
Emmanuel, M.A., Greenberg, N.R., Oblinsky, D.G. and Hyster, T.K. (2016) Accessing Non-Natural Reactivity by Irradiating Nicotinamide-Dependent Enzymes with Light. Nature, 540, 414-417. https://doi.org/10.1038/nature20569
[29]
Peng, Y., Wang, Z., Chen, Y., Xu, W., Hu, Y., Chen, Z., et al. (2022) Photoinduced Promiscuity of Cyclohexanone Monooxygenase for the Enantioselective Synthesis of α‐Fluoroketones. Angewandte Chemie International Edition, 61, e202211199. https://doi.org/10.1002/anie.202211199
[30]
Ye, Y., Cao, J., Oblinsky, D.G., Verma, D., Prier, C.K., Scholes, G.D., et al. (2022) Using Enzymes to Tame Nitrogen-Centred Radicals for Enantioselective Hydroamination. Nature Chemistry, 15, 206-212. https://doi.org/10.1038/s41557-022-01083-z
[31]
Chen, X., Zheng, D., Jiang, L., Wang, Z., Duan, X., Cui, D., et al. (2023) Photoenzymatic Hydrosulfonylation for the Stereoselective Synthesis of Chiral Sulfones. Angewandte Chemie International Edition, 62, e202218140. https://doi.org/10.1002/anie.202218140
[32]
Shi, Q., Kang, X., Liu, Z., Sakthivel, P., Aman, H., Chang, R., et al. (2024) Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis. Journal of the American Chemical Society, 146, 2748-2756. https://doi.org/10.1021/jacs.3c12513
[33]
van Schie, M.M.C.H., Paul, C.E., Arends, I.W.C.E. and Hollmann, F. (2019) Photoenzymatic Epoxidation of Styrenes. Chemical Communications, 55, 1790-1792. https://doi.org/10.1039/c8cc08149b
[34]
Höfler, G.T., Fernández‐Fueyo, E., Pesic, M., Younes, S.H., Choi, E., Kim, Y.H., et al. (2018) A Photoenzymatic NADH Regeneration System. ChemBioChem, 19, 2344-2347. https://doi.org/10.1002/cbic.201800530
[35]
Cesana, P.T., Page, C.G., Harris, D., Emmanuel, M.A., Hyster, T.K. and Schlau-Cohen, G.S. (2022) Photoenzymatic Catalysis in a New Light: Gluconobacter “Ene”-Reductase Conjugates Possessing High-Energy Reactivity with Tunable Low-Energy Excitation. Journal of the American Chemical Society, 144, 17516-17521. https://doi.org/10.1021/jacs.2c06344
[36]
Zhang, W., Ma, M., Huijbers, M.M.E., Filonenko, G.A., Pidko, E.A., van Schie, M., et al. (2019) Hydrocarbon Synthesis via Photoenzymatic Decarboxylation of Carboxylic Acids. Journal of the American Chemical Society, 141, 3116-3120. https://doi.org/10.1021/jacs.8b12282
[37]
Li, X., Page, C.G., Zanetti-Polzi, L., Kalra, A.P., Oblinsky, D.G., Daidone, I., et al. (2023) Mechanism and Dynamics of Photodecarboxylation Catalyzed by Lactate Monooxygenase. Journal of the American Chemical Society, 145, 13232-13240. https://doi.org/10.1021/jacs.3c02446
[38]
Yang, H., Impano, S., Shepard, E.M., James, C.D., Broderick, W.E., Broderick, J.B., et al. (2019) Photoinduced Electron Transfer in a Radical SAM Enzyme Generates an S-Adenosylmethionine Derived Methyl Radical. Journal of the American Chemical Society, 141, 16117-16124. https://doi.org/10.1021/jacs.9b08541
[39]
Zippilli, C., Bartolome, M.J., Hilberath, T., Botta, L., Hollmann, F. and Saladino, R. (2022) A Photochemoenzymatic Hunsdiecker‐Borodin‐Type Halodecarboxylation of Ferulic Acid. ChemBioChem, 23, e202200367. https://doi.org/10.1002/cbic.202200367
[40]
Wang, Y., Liu, H., Pan, Q., Wu, C., Hao, W., Xu, J., et al. (2020) Construction of Fully Conjugated Covalent Organic Frameworks via Facile Linkage Conversion for Efficient Photoenzymatic Catalysis. Journal of the American Chemical Society, 142, 5958-5963. https://doi.org/10.1021/jacs.0c00923
[41]
Zhang, B., Yu, Y., Fox, B.W., Liu, Y., Thirumalaikumar, V.P., Skirycz, A., et al. (2024) Amino Acid and Protein Specificity of Protein Fatty Acylation in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 121, e2307515121. https://doi.org/10.1073/pnas.2307515121
