A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural...

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Organic Synthesis

Background:

• High-throughput screening (HTS) is crucial for identifying drug leads.
• Current screening libraries lack structural and stereochemical complexity, limiting drug target modulation.
• Natural products offer a rich source of complex chemical scaffolds.

Purpose of the Study:

• To develop a novel strategy for generating diverse, complex compounds.
• To utilize natural products as starting materials for synthetic compound libraries.
• To enhance the chemical space accessible for drug discovery.

Main Methods:

• A general and facile synthetic strategy was developed.
• Readily available natural products were employed as starting points.
• Chemical properties (fraction of sp3 carbons, ClogP, stereogenic centers) were evaluated.

Main Results:

• The strategy successfully created diverse compounds with high structural and stereochemical complexity.
• Generated compounds exhibit significantly greater complexity than standard screening collections.
• Guidelines for applying the strategy to various natural products were established.

Conclusions:

• This approach provides a powerful method to expand screening libraries with complex, drug-like molecules.
• Utilizing natural products enhances the potential for discovering novel therapeutics.
• The strategy offers a versatile platform for medicinal chemistry efforts.