Functional Group Tolerance of a Micellar on-DNA Suzuki-Miyaura Cross-Coupling Reaction for DNA-Encoded Library Design

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Biotechnology

Background:

• DNA-encoded libraries (DELs) are powerful tools for identifying novel protein ligands.
• Current DEL synthesis methods often face limitations with substrate scope and reaction efficiency.
• Developing versatile and high-fidelity synthetic strategies is crucial for expanding DEL applications.

Purpose of the Study:

• To develop an improved method for synthesizing DNA-encoded libraries (DELs).
• To enhance the diversity and fidelity of DELs through optimized reaction conditions.
• To demonstrate the broad applicability and functional group tolerance of the proposed synthetic strategy.

Main Methods:

• Utilized a combination of multicomponent reactions for initial library construction.
• Employed micellar-promoted Suzuki-Miyaura cross-coupling for subsequent diversification.
• Investigated the reaction's efficiency and fidelity across a wide range of substrates.

Main Results:

• Successfully synthesized highly diverse DNA-encoded libraries.
• Achieved exceptionally high fidelity in DEL synthesis using the micellar Suzuki-Miyaura reaction.
• Demonstrated broad substrate scope and excellent functional group tolerance for the micellar Suzuki-Miyaura reaction.

Conclusions:

• The micellar Suzuki-Miyaura cross-coupling reaction is a versatile and efficient method for DEL synthesis.
• This approach significantly enhances the diversity and fidelity of DELs.
• The demonstrated functional group tolerance and broad applicability pave the way for discovering new protein ligands.