Synthetic entries to substituted bicyclic pyridones

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Bicyclic pyridone scaffolds are important structural motifs in medicinal chemistry.
• Efficient synthetic routes to functionalized bicyclic pyridones are crucial for drug discovery and development.

Purpose of the Study:

• To develop a novel and efficient synthesis of 6,6- and 5,6-bicyclic pyridone scaffolds.
• To achieve regioselective functionalization of these scaffolds.
• To introduce aryl units onto the bicyclic pyridone core.

Main Methods:

• Intramolecular Mitsunobu reaction for scaffold formation.
• Hydrolysis of bicyclic pyridinium salt intermediates.
• Regioselective functionalization via direct lithiation or "halogen dance" reaction.
• Suzuki coupling for aryl unit introduction.

Main Results:

• Successful synthesis of 6,6- and 5,6-bicyclic pyridone scaffolds.
• Demonstrated regioselective functionalization at specific positions.
• Effective introduction of diverse aryl units using Suzuki coupling, particularly with iodopyridinium intermediates.

Conclusions:

• The developed synthetic strategy provides access to a range of functionalized bicyclic pyridone scaffolds.
• The methodology allows for late-stage diversification, facilitating the exploration of structure-activity relationships.
• These scaffolds serve as valuable intermediates for the synthesis of potential therapeutic agents.