Jin Wang, Han Ke, Jun Yang, Nianxin Guo, Kangdelong Hu, Ruyao Tang, Qi Ding, Lei Gao,*and Xiaoguang Lei*
Chem Catalysis 3, 1–12, January 19, 2023
https://doi.org/10.1016/j.checat.2022.10.027
Substituted cyclohexanes are common scaffolds found in both natural products and drug molecules. Diels-Alderases that can efficiently catalyze intermolecular Diels-Alder reactions to generate cyclohexene ring systems have received considerable interest. However, the synthetic power of Diels-Alderases is incomparable with chemo-catalysts due to their limited substrate scopes. Here, we report a new chemo-enzymatic strategy for the diversity-oriented syntheses of functionalized cyclohexenes. We first applied focused rational iterative site-specific mutagenesis to generate a natural Diels-Alderase variant M3, which shows a 34-fold increase in catalytic efficiency,
broad substrate scope, and good to perfect stereoselectivity.Then, we used diverse transition-metal-catalyzed decarboxylative coupling reactions to functionalize the enzymatic Diels-Alder products.This work offers an efficient synthetic route to structurally diverse cyclohexenes that are not accessible by solely using biocatalysis or chemo-catalysis and illustrates how chemo-catalysis can cooperate with biocatalysis to expand the synthetic application
of biocatalysts.
Jin Wang, Han Ke, Jun Yang, Nianxin Guo, Kangdelong Hu, Ruyao Tang, Qi Ding, Lei Gao,*and Xiaoguang Lei*
Chem Catalysis 3, 1–12, January 19, 2023
https://doi.org/10.1016/j.checat.2022.10.027
Substituted cyclohexanes are common scaffolds found in both natural products and drug molecules. Diels-Alderases that can efficiently catalyze intermolecular Diels-Alder reactions to generate cyclohexene ring systems have received considerable interest. However, the synthetic power of Diels-Alderases is incomparable with chemo-catalysts due to their limited substrate scopes. Here, we report a new chemo-enzymatic strategy for the diversity-oriented syntheses of functionalized cyclohexenes. We first applied focused rational iterative site-specific mutagenesis to generate a natural Diels-Alderase variant M3, which shows a 34-fold increase in catalytic efficiency,
broad substrate scope, and good to perfect stereoselectivity.Then, we used diverse transition-metal-catalyzed decarboxylative coupling reactions to functionalize the enzymatic Diels-Alder products.This work offers an efficient synthetic route to structurally diverse cyclohexenes that are not accessible by solely using biocatalysis or chemo-catalysis and illustrates how chemo-catalysis can cooperate with biocatalysis to expand the synthetic application
of biocatalysts.