Enzymatic Oxy‐ and Amino‐Functionalization in Biocatalytic Cascade Synthesis: Recent Advances and Future Perspectives

Abstract

Biocatalytic cascades are a powerful tool for building complex molecules containing oxygen and nitrogen functionalities. Moreover, the combination of multiple enzymes in one pot offers the possibility to minimize downstream processing and waste production. In this review, we illustrate various recent efforts in the development of multi‐step syntheses involving C−O and C−N bond‐forming enzymes to produce high value‐added compounds, such as pharmaceuticals and polymer precursors. Both in vitro and in vivo examples are discussed, revealing the respective advantages and drawbacks. The use of engineered enzymes to boost the cascades outcome is also addressed and current co‐substrate and cofactor recycling strategies are presented, highlighting the importance of atom economy. Finally, tools to overcome current challenges for multi‐enzymatic oxy‐ and amino‐functionalization reactions are discussed, including flow systems with immobilized biocatalysts and cascades in confined nanomaterials.

Developing Hybrid Systems to Address O2Uncoupling in Multi-Component Rieske Oxygenases

“…The oxyfunctionalization of C-H bonds in organic molecules is an essential reaction catalyzed by various enzymes, including peroxygenases or oxygenases. [1][2][3] Unlike peroxygenases, which, as their name implies, utilize H 2 O 2 , 4 the latter class of enzymes is capable of (also) utilizing molecular oxygen to activate unreactive or inert molecular structures for late-stage modifications. 5 In addition to their outstanding catalytic performance in terms of selectivity and reaction rates, oxygenases have become an indispensable tool in the design of biotechnological applications such as bioremediation, 6 lignocellulose combustion, 7 or (biocatalytic) synthesis.…”

Copper/Iodine Co-catalyzed Oxygenative Transannulation of Tryptamines Enables Direct Synthesis of Donaxaridine and Its Derivatives

“…Oxygen-containing molecules are ubiquitous in natural products and bioactive compounds. These molecules are frequently used as organic synthons in the synthesis of functionalized products . The preparation of these molecules has attracted a great deal of interest from organic chemists.…”