What's new in enzymatic halogenations
Danica Galonić Fujimori1, Christopher T Walsh
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Abstract:
The halogenation of thousands of natural products occurs during biosynthesis and often confers important functional properties. While haloperoxidases had been the default paradigm for enzymatic incorporation of halogens, via X+ equivalents into organic scaffolds, a combination of microbial genome sequencing, enzymatic studies and structural biology have provided deep new insights into enzymatic transfer of halide equivalents in three oxidation states. These are (1) the halide ions (X-) abundant in nature, (2) halogen atoms (X*), and (3) the X+ equivalents. The mechanism of halogen incorporation is tailored to the electronic demands of specific substrates and involves enzymes with distinct redox coenzyme requirements.
Related Concept Videos
Halogenation of Alkenes
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Electrophilic Addition to Alkynes: Hydrohalogenation
Base-Promoted α-Halogenation of Aldehydes and Ketones
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
Reactions at the Benzylic Position: Halogenation
Radical Halogenation: Thermodynamics

