Synthesis of β-Quaternary Lactams Using Photoenzymatic Catalysis

Area of Science:

• Organic Chemistry
• Biocatalysis
• Synthetic Chemistry

Background:

• Quaternary carbons are valuable synthetic building blocks.
• Traditional methods for their synthesis are often inefficient or lack stereoselectivity.
• Biocatalysis offers a promising alternative for complex molecule synthesis.

Purpose of the Study:

• To develop a stereoselective synthesis of beta-quaternary lactams.
• To explore the use of flavin-dependent 'ene'-reductases in radical cyclization reactions.
• To demonstrate the potential of biocatalysis for creating quaternary carbon centers.

Main Methods:

• Utilized flavin-dependent 'ene'-reductases for a 5-exo-trig radical cyclization.
• Employed a specific 'ene'-reductase variant from Zymomonas mobilis.
• Investigated the stereoselectivity of the biocatalytic transformation.

Main Results:

• Achieved a stereoselective synthesis of beta-quaternary lactams.
• Products were obtained in moderate to good enantioselectivity.
• Demonstrated the feasibility of using biocatalysis for non-natural reactions.

Conclusions:

• Biocatalysis, specifically using flavin-dependent 'ene'-reductases, provides an effective route to beta-quaternary lactams.
• This method offers a stereoselective approach to constructing challenging quaternary carbon centers.
• Highlights the potential of enzyme engineering for novel synthetic transformations.