Abstract
Biocatalytic dearomatisation offers the advantages of high chemo-, regio- and stereoselectivity
over chemical strategies. Mono- and dioxygenases with dearomatising properties are
already well-established tools for the synthesis of natural products and beyond. Herein,
we review investigations of protein sequence–activity relationships, as well as protein-engineering
approaches that have been employed to expand the substrate scope of biocatalysts and
achieve product regio- and stereodiversity. Thus, oxidative dearomatising biocatalysts
offer an increasingly diverse toolbox for the synthesis of asymmetric, oxidised cyclic
scaffolds, as illustrated through selected examples of biocatalytic applications in
synthetic routes towards natural products and derivatives thereof. Reductases with
dearomatising properties have been less well investigated, so we review recent mechanistic
findings which, henceforth, allow for expanding applications of this class of biocatalysts.
Additionally, chemoenzymatic strategies have been developed to overcome the limitations
of purely biocatalytic or chemical dearomatisation approaches. We highlight examples
of those combination strategies for the synthesis of asymmetric privileged motifs.
1 Introduction
2 Oxidative Biocatalytic Dearomatisation
3 Reductive Biocatalytic Dearomatisation
4 Chemoenzymatic Dearomatisation
5 Conclusion
Key words
biocatalysis - dearomatisation - enzymes - protein engineering - oxidative
