To control unruly radicals, sometimes mother knows best. Tapping into nature, Huimin Zhao and coworkers at the University of Illinois at Urbana-Champaign and Xiamen University in China have created a new enzymatic reaction that uses light to stereoselectively couple two carbon compounds (Nature 2020, DOI: 10.1038/s41586-020-2406-6). The reaction creates gamma chiral carbonyls, with ketones or esters, in 47 to 99% yields and with an enantiomeric selectivity of 93 to 99% (example shown). These types of terminal alkanes are difficult to make but found in many bioactive compounds, Zhao says. He and his team identified a class of enzymes called ene-reductases that can catalyze their target reaction. After optimizing the reaction, the researchers found that the known enzyme, old yellow enzyme 1, gave the highest yields of the product, with 96% enantiomeric selectivity, which surprised Zhao. “In an intramolecular coupling reaction, it’s hard to control the selectivity,” he says. Here, the enzyme provides a reaction vessel, forming only one enantiomer. The group proposes that the reaction has a novel, radical mechanism. The enzyme holds the reactants close to each other and stabilizes the radicals. The reaction is new to nature, Zhao says. Photoactive enzymes work under mild conditions and can access reactions elusive to chemical catalysts. This ene-reductase is so far the only catalyst that can do this selective reaction. Zhao thinks there may be more opportunities with similar chemistry. “There are many other flavin enzymes out there that are photoactive as well,” he says.
This story was updated on June 25, 2020, to correct the journal name. The study was published in Nature, not Science.