Diversity-oriented photobiocatalytic synthesis via stereoselective three-component radical coupling

Area of Science:

• Organic Chemistry
• Biocatalysis
• Medicinal Chemistry

Background:

• Enzymatic multicomponent reactions for diversity-oriented synthesis are limited.
• Stereoselective radical-mediated C-C bond formation is challenging in biocatalysis.

Purpose of the Study:

• To develop a novel enzymatic platform for stereoselective three-component C-C bond forming reactions.
• To enable diversity-oriented synthesis using cooperative photobiocatalysis.

Main Methods:

• Utilized cooperative photobiocatalysis for a three-component radical-mediated C-C coupling.
• Employed directed evolution of pyridoxal decarboxylases to enhance fragment variability.
• Integrated principles of asymmetric catalysis, including remote stereocenter construction and kinetic resolution.

Main Results:

• Achieved a novel stereoselective three-component radical-mediated C-C coupling reaction.
• Demonstrated full fragment variability with six classes of valuable products.
• Attained excellent diastereeo- and enantiocontrol over radical intermediates.
• Enabled combinatorial library synthesis of diverse molecular scaffolds.

Conclusions:

• The developed enzymatic platform provides a powerful tool for diversity-oriented synthesis.
• This method offers access to complex molecular scaffolds previously unattainable.
• The approach integrates multiple asymmetric catalysis principles for precise stereochemical control.