References
Purser, S., Moore, P. R., Swallow, S. & Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 37, 320–330 (2008).
O’Hagan, D. Understanding organofluorine chemistry. An introduction to the C–F bond. Chem. Soc. Rev. 37, 308–319 (2008).
Inoue, M., Sumii, Y. & Shibata, N. Contribution of organofluorine compounds to pharmaceuticals. ACS Omega 5, 10633–10640 (2020).
Benedetto Tiz, D. et al. New halogen-containing drugs approved by FDA in 2021: an overview on their syntheses and pharmaceutical use. Molecules 27, 1643 (2022).
Britton, R. et al. Contemporary synthetic strategies in organofluorine chemistry. Nat. Rev. Methods Primers 1, 47 (2021).
Furuya, T., Kamlet, A. S. & Ritter, T. Catalysis for fluorination and trifluoromethylation. Nature 473, 470–477 (2011).
Yang, X. Y., Wu, T., Phipps, R. J. & Toste, F. D. Advances in catalytic enantioselective fluorination, mono-, di-, and trifluoromethylation, and trifluoromethylthiolation reactions. Chem. Rev. 115, 826–870 (2015).
Caron, S. Where does the fluorine come from? A review on the challenges associated with the synthesis of organofluorine compounds. Org. Process Res. Dev. 24, 470–480 (2020).
Walker, M. C. & Chang, M. C. Y. Natural and engineered biosynthesis of fluorinated natural products. Chem. Soc. Rev. 43, 6527–6536 (2014).
O’Hagan, D. & Deng, H. Enzymatic fluorination and biotechnological developments of the fluorinase. Chem. Rev. 115, 634–649 (2015).
Vaillancourt, F. H., Yeh, E., Vosburg, D. A., Garneau-Tsodikova, S. & Walsh, C. T. Nature’s inventory of halogenation catalysts: oxidative strategies predominate. Chem. Rev. 106, 3364–3378 (2006).
Agarwal, V. et al. Enzymatic halogenation and dehalogenation reactions: pervasive and mechanistically diverse. Chem. Rev. 117, 5619–5674 (2017).
Papadopoulou, A., Meyer, F. & Buller, R. M. Engineering Fe(II)/α-ketoglutarate-dependent halogenases and desaturases. Biochemistry 62, 229–240 (2023).
Dong, C. et al. Crystal structure and mechanism of a bacterial fluorinating enzyme. Nature 427, 561–565 (2004).
O’Hagan, D., Schaffrath, C., Cobb, S. L., Hamilton, J. T. G. & Murphy, C. D. Biosynthesis of an organofluorine molecule—a fluorinase enzyme has been discovered that catalyses carbon–fluorine bond formation. Nature 416, 279 (2002).
Zechel, D. L. et al. Enzymatic synthesis of carbon–fluorine bonds. J. Am. Chem. Soc. 123, 4350–4351 (2001).
Cros, A., Alfaro-Espinoza, G., De Maria, A., Wirth, N. T. & Nikel, P. I. Synthetic metabolism for biohalogenation. Curr. Opin. Biotechnol. 74, 180–193 (2022).
Cheng, X. & Ma, L. Enzymatic synthesis of fluorinated compounds. Appl. Microbiol. Biotechnol. 105, 8033–8058 (2021).
Eustáquio, A. S., O’Hagan, D. & Moore, B. S. Engineering fluorometabolite production: fluorinase expression in salinispora tropica yields fluorosalinosporamide. J. Nat. Prod. 73, 378–382 (2010).
Liu, W. & Groves, J. T. Manganese catalyzed C–H halogenation. Acc. Chem. Res. 48, 1727–1735 (2015).
Panda, C., Anny-Nzekwue, O., Doyle, L. M., Gericke, R. & McDonald, A. R. Evidence for a high-valent iron-fluoride that mediates oxidative C(sp3)–H fluorination. JACS Au 3, 919–928 (2023).
Farley, G. W., Siegler, M. A. & Goldberg, D. P. Halogen transfer to carbon radicals by high-valent iron chloride and iron fluoride corroles. Inorg. Chem. 60, 17288–17302 (2021).
Bower, J. K., Cypcar, A. D., Henriquez, B., Stieber, S. C. E. & Zhang, S. C(sp3)–H fluorination with a copper(II)/(III) redox couple. J. Am. Chem. Soc. 142, 8514–8521 (2020).
Huang, X., Liu, W., Hooker, J. M. & Groves, J. T. Targeted fluorination with the fluoride ion by manganese-catalyzed decarboxylation. Angew. Chem. Int. Ed. 54, 5241–5245 (2015).
Huang, X. et al. Late stage benzylic C–H fluorination with [18F]fluoride for PET imaging. J. Am. Chem. Soc. 136, 6842–6845 (2014).
Liu, W. & Groves, J. T. Manganese-catalyzed oxidative benzylic C–H fluorination by fluoride ions. Angew. Chem. Int. Ed. 52, 6024–6027 (2013).
Liu, W. et al. Oxidative aliphatic C–H fluorination with fluoride ion catalyzed by a manganese porphyrin. Science 337, 1322–1325 (2012).
Pinter, E. N., Bingham, J. E., AbuSalim, D. I. & Cook, S. P. N-directed fluorination of unactivated Csp3–H bonds. Chem. Sci. 11, 1102–1106 (2020).
Groendyke, B. J., AbuSalim, D. I. & Cook, S. P. Iron-catalyzed, fluoroamide-directed C–H fluorination. J. Am. Chem. Soc. 138, 12771–12774 (2016).
Hintz, H. et al. Copper-catalyzed electrochemical C–H fluorination. Chem Catal. 3, 100491 (2023).
Rui, J. et al. Directed evolution of nonheme iron enzymes to access abiological radical-relay C(sp3)–H azidation. Science 376, 869–874 (2022).
Liu, P. et al. Protein purification and function assignment of the epoxidase catalyzing the formation of fosfomycin. J. Am. Chem. Soc. 123, 4619–4620 (2001).
Wang, C. et al. Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase. Science 342, 991–995 (2013).
Mitchell, A. J. et al. Structure-guided reprogramming of a hydroxylase to halogenate its small molecule substrate. Biochemistry 56, 441–444 (2017).
Gomez, C. A., Mondal, D., Du, Q., Chan, N. & Lewis, J. C. Directed evolution of an iron(II)- and α-ketoglutarate-dependent dioxygenase for site-selective azidation of unactivated aliphatic C–H bonds. Angew. Chem. Int. Ed. 62, e202301370 (2023).
Neugebauer, M. E. et al. Reaction pathway engineering converts a radical hydroxylase into a halogenase. Nat. Chem. Biol. 18, 171–179 (2022).
Papadopoulou, A. et al. Re-programming and optimization of a l-proline cis-4-hydroxylase for the cis-3-halogenation of its native substrate. ChemCatChem 13, 3914–3919 (2021).
Olivares, P., Ulrich, E. C., Chekan, J. R., van der Donk, W. A. & Nair, S. K. Characterization of two late-stage enzymes involved in fosfomycin biosynthesis in pseudomonads. ACS Chem. Biol. 12, 456–463 (2017).
Yun, D. et al. Structural basis of regiospecificity of a mononuclear iron enzyme in antibiotic fosfomycin biosynthesis. J. Am. Chem. Soc. 133, 11262–11269 (2011).
Higgins, L. J., Yan, F., Liu, P. H., Liu, H. W. & Drennan, C. L. Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron enzyme. Nature 437, 838–844 (2005).
Tarantino, G. & Hammond, C. Catalytic C(sp3)–F bond formation: recent achievements and pertaining challenges. Green Chem. 22, 5195–5209 (2020).
Matthews, M. L. et al. Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2. Proc. Natl Acad. Sci. USA 106, 17723–17728 (2009).
Kulik, H. J. & Drennan, C. L. Substrate placement influences reactivity in non-heme Fe(II) halogenases and hydroxylases. J. Biol. Chem. 288, 11233–11241 (2013).
Kissman, E. N. et al. Biocatalytic control of site-selectivity and chain length-selectivity in radical amino acid halogenases. Proc. Natl Acad. Sci. USA 120, e2214512120 (2023).
Chan, N. H. et al. Non-native anionic ligand binding and reactivity in engineered variants of the Fe(II)- and α-ketoglutarate-dependent oxygenase, SadA. Inorg. Chem. 61, 14477–14485 (2022).
Dai, L. et al. Structural and functional insights into a nonheme iron- and α-ketoglutarate-dependent halogenase that catalyzes chlorination of nucleotide substrates. Appl. Environ. Microbiol. 88, e02497–02421 (2022).
Kastner, D. W., Nandy, A., Mehmood, R. & Kulik, H. J. Mechanistic insights into substrate positioning that distinguish non-heme Fe(II)/α-ketoglutarate-dependent halogenases and hydroxylases. ACS Catal. 13, 2489–2501 (2023).
