One-Pot Synthesis of Tricyclic Benzoxazines and Benzoxazepine by Heterogeneous Biochemo Multienzyme Cascade Reaction

Area of Science:

• Organic Chemistry
• Biocatalysis
• Green Chemistry

Background:

• Conventional synthesis of complex heterocyclic compounds often involves multiple steps, harsh reagents, and significant waste generation.
• Developing sustainable and efficient synthetic methodologies is crucial for modern chemical research and industrial applications.

Purpose of the Study:

• To develop a novel, one-pot, enzyme-catalyzed method for synthesizing benzoxazine and benzoxazepine derivatives.
• To explore the application of a biochemo multienzyme cascade involving lipase M and tyrosinase for heterocyclic synthesis.
• To establish a sustainable and atom-economical alternative to traditional synthetic routes.

Main Methods:

• A one-pot biochemo multienzyme cascade reaction was employed, utilizing lipase M and tyrosinase.
• The cascade involved tyrosinase-mediated *ortho*-hydroxylation of phenolic compounds.
• Subsequent steps included a 1,6-Michael addition and tandem intramolecular ring closure to form the target derivatives.

Main Results:

• Efficient synthesis of various benzoxazine and benzoxazepine derivatives with tricyclic lactone and lactam rings was achieved.
• The reaction demonstrated high atom economy and significantly reduced the number of purification steps.
• The enzymes, lipase M and tyrosinase, exhibited excellent reusability, underscoring the green nature of the process.

Conclusions:

• The developed one-pot multienzyme cascade offers a sustainable and efficient approach for synthesizing valuable heterocyclic compounds.
• This biocatalytic method represents a greener alternative to conventional multistep syntheses, aligning with the principles of green chemistry.
• The reusability of enzymes highlights the economic and environmental benefits of this innovative synthetic strategy.