Biocatalytic Redox Reactions for Organic Synthesis: Nonconventional Regeneration Methods

Redox enzymes have tremendous potential as catalysts for preparative organic chemistry. Their usually high selectivity, paired with their catalytic efficiency under mild reaction conditions, makes them potentially very valuable tools for synthesis. The number of interesting monooxygenases, dehydrogenases, reductases, oxidases, and peroxidases is steadily increasing and the tailoring of a given biocatalyst is more and more becoming standard technology. However, their cofactor dependency still represents a major impediment en route to true preparative applicability. Currently, three different approaches to deal with this ‘cofactor challenge’ are being pursued: using whole cells, biomimetic approaches comprising enzymatic cofactor regenerations systems, and ‘unconventional’ nonenzymatic regeneration. The latter technique offers the promise of enabling simple, easily applicable, and robust reaction schemes, for example, by circumventing the ‘cofactor challenge’ and introducing redox power directly to the enzyme’s active sites. Oxidoreductases represent a preparatively highly interesting class of biocatalysts. However, to sustain the catalytic cycle, electrons must constantly be provided to or withdrawn from the enzymes. Alongside well‐established enzymatic methodologies, unconventional chemical alternatives have been developed recently. These approaches are summarized herein and their potential is critically reviewed.