Enzymatic Synthesis of Saturated Bioisosteres of Ortho-Substituted Benzenes by Artificial Photoenzyme.

Saturated bioisosteres of ortho-substituted benzenes are of significant interest due to their enhanced pharmacokinetic properties, such as improved metabolic stability and reduced toxicity, making them valuable in drug design and development. However, efficient synthesis of them remains a challenge in organic chemistry. Herein, we report the biocatalytic synthesis of saturated bioisosteres of ortho-substituted benzenes using engineered artificial photoenzymes. The artificial photoenzyme, incorporating genetically encoded unnatural amino acids with benzophenone photosensitizer residue, facilitate the formation of chiral saturated bioisosteres with moderate enantiomeric excess via the energy transfer process. Our results demonstrate the versatility of artificial photoenzymes in mediating new-to-nature reactions that are difficult to achieve with conventional chemical or enzymatic methods.