2025-09-03 カリフォルニア大学サンタバーバラ校(UCSB)
<関連情報>
- https://news.ucsb.edu/2025/022011/new-catalysis-method-can-generate-library-novel-molecules-drug-discovery
- https://www.science.org/doi/10.1126/science.adx2935
立体選択的三重ラジカルカップリングによる多様性指向型光生物触媒合成 Diversity-oriented photobiocatalytic synthesis via stereoselective three-component radical coupling
Chen Zhang, Jun Zhou, Pei-Pei Xie, Silvia M. Rivera, […] , and Yang Yang
Science Published:31 Jul 2025
DOI:https://doi.org/10.1126/science.adx2935
Abstract
Enzymatic multicomponent C–C bond forming reactions for diversity-oriented synthesis remain rare. Using cooperative photobiocatalysis, we developed a stereoselective three-component radical-mediated C–C coupling unknown in both organic chemistry and biochemistry. Directed evolution of repurposed pyridoxal decarboxylases enabled full fragment variability in this three-component coupling, giving rise to six classes of valuable products, many of which were inaccessible by other methods, even in a racemic fashion. This enzymatic platform integrates a range of asymmetric catalysis principles, including remote stereocenter construction, stereodivergent catalysis, kinetic resolution and parallel kinetic resolution, achieving excellent diastereo- and enantiocontrol over radical intermediates. The broad substrate scope and complementary specificities of evolved enzyme variants enabled combinatorial library synthesis, affording structurally and stereochemically diverse scaffolds for medicinal chemistry.
