Enzymatic Halogenation: A Timely Strategy for Regioselective C−H Activation

5 years ago

Enzymatic Halogenation: A Timely Strategy for Regioselective C−H Activation

Norbert Sewald, Christian Schnepel

Halogenating enzymes are increasingly attracting attention for biocatalytic C−H functionalization. Despite its importance for synthetic chemistry, selective introduction of halogens using conventional approaches often remains challenging, whereas biocatalysis offers excellent catalyst-controlled selectivity without requiring protecting groups or hazardous reagents. Owing to the high prevalence of halogenated secondary metabolites, a still growing repertoire of halogenases has been identified. Recently, flavin-dependent tryptophan halogenases came into focus for synthetic use. Nevertheless, these enzymes still suffer from severe deficiencies. Herein, current attempts in optimizing tryptophan halogenases have been compiled. Enzyme discovery, structure elucidation and mechanisms are reviewed with focus on biosynthesis of halogenated arenes. Emphasis is also given to random and rational engineering, high-throughput screening and implementation of halogenases into one-pot processes. New recipes for biohalogenation: Enzymatic halogenation has developed to a sustainable synthetic tool for catalyst-controlled C−H activation. Predominantly flavin-dependent tryptophan halogenases have been explored and engineered to make these biocatalysts accessible for synthesis. Recent achievements with emphasis on improving the synthetic utility, directed evolution, and one-pot cross-coupling are provided.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701209