One-pot synthesis of tricyclic benzoxazines and benzoxazepine by heterogeneous biochemo multienzyme cascade reaction

Benzoxazine and benzoxazepine derivatives with tricyclic five-, six-, and seven-membered lactone and lactam rings were synthesized in one-pot conditions by using biochemo multienzyme cascade of lipase M and tyrosinase. The reaction involves tyrosinase-mediated ortho-hydroxylation of the phenolic moiety, followed by 1,6-Michael addition and tandem intramolecular ring closure. The method achieves high atom economy, minimizes purification steps, and provides a sustainable alternative to conventional multistep syntheses. Enzymes showed excellent reusability, further enhancing the green approach.