Harnessing the biocatalytic potential of iron- and α-ketoglutarate-dependent dioxygenases in natural product total synthesis.

Covering: up to the end of 2019Iron- and α-ketoglutarate-dependent dioxygenases (Fe/αKGs) represent a versatile and intriguing enzyme family by virtue of their ability to directly functionalize unactivated C-H bonds at the cost of αKG and O. Fe/αKGs play an important role in the biosynthesis of natural products, valuable biologically active secondary metabolites frequently pursued as drug leads. The field of natural product total synthesis seeks to contruct these molecules as effeciently as possible, although natural products continue to challenge chemists due to their intricate structural complexity. Chemoenzymatic approaches seek to remedy the shortcomings of traditional synthetic methodology by combining Nature's biosynthetic machinery with traditional chemical methods to efficiently construct natural products. Although other oxygenase families have been widely employed for this purpose, Fe/αKGs remain underutilized. The following review will cover recent chemoenzymatic total syntheses involving Fe/αKG enzymes. Additionally, related information involving natural product biosynthesis, methods development, and non-chemoenzymatic total syntheses will be discussed to inform retrosynthetic logic and synthetic design.