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Enzyme-catalysed Halogenation

Mechanism + Description

A number of enzymes are known to catalyze halogenation, with chlorination being the most prevalent reaction. Some enzymes (haloperoxidases) generate HOX from the corresponding halide, with oxygen being the terminal oxidant. Reactivity follows that of free HOX.

Halogenases keep the Cl+ equivalent bound to an oxidized flavin in the enzyme active site and are thus much more selective with respect to the regioselectivity of chlorination. Some newer classes of halogenating enzymes seem to react via a radical mechanism.

General comments

There is a growing interest in halogenation using enzymes, although this technology is not yet scaled and is currently limited to fairly electron-rich substrates like tryptophans and pyrroles.

Key references

Vaillaincourt, F. H.; Yeh, E.; Vosburg, D. A.; Garneau-Tsodikova, S.; Walsh, C. T. Nature’s Inventory of Halogenation Catalysts: Oxidative Strategies Predominate. Chem. Rev. 2006, 106(8), 3364−3378.

Smith, D. R. M.; Grüschow, S.; Goss, R. J. M. Scope and potential of halogenases in biosynthetic applications. Current Opinion in Chemical Biology. 2013, 17(2),1–8.

Mahoney, K. P. P.; Smith, D. R. M.; Bogosyan, E. J. A.; Goss, R. J. M. Access to High Value Natural and Unnatural Products through Hyphenating Chemical Synthesis and Biosynthesis. Synthesis. 2014, 46(16), 2122-2132.

Van Pée, K. Chapter Twelve –  Enzymatic chlorination and bromination. Chemical Synthesis and Biosynthesis Methods Enzymol. 2012, 516, 237-257.