Halogenases for the synthesis of small molecules

Discovery and substrate specificity engineering of nucleotide halogenases

“…Late-stage functionalization of C−H bonds has proven to be an efficient method for modifying complex molecules [1][2][3][4][5] . Among the various reactions in this field, late-stage C−H halogenation is particularly valuable as it allows for the manipulation of bioactivity and the installation of reactive handles for subsequent transformations 6,7 . Despite intense efforts, the halogenation of unactivated sp 3 C−H bonds remains a challenging task due to the difficulties in finding a catalyst that enables high reactivity and selectivity under mild reaction conditions.…”

Decarboxylative halogenation of indoles by vanadium haloperoxidases

“…Enzymes are attractive catalyst systems for selective halogenation reactions as a result of their comparatively mild operational parameters relative to small molecule catalysts. Amongst the host of halogenases that have been applied to the halogenation of small molecules, 5 the vanadium haloperoxidase (VHPO) class of enzymes has emerged as viable catalysts for halogenation reactions on a range of electron-rich substrate types. 6,7 In the context of decarboxylative halogenation reactions, the VHPOs have been applied in reports of a decarboxylative bromination of cinnamic acids by Hollmann 8 and in the context of a decarboxylative bromooxidation of 3-carboxyindoles by our laboratory.…”