A versatile synthetic approach toward diversity libraries using monosaccharide scaffolds.

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Drug Discovery

Background:

• The pyranose scaffold offers unique 3D positioning of pharmacophore substituents.
• Existing methods allow substituent diversity but lack precise spatial control.
• Generating libraries of pyranose-based drug-like mimetics with defined pharmacophore positions is desirable.

Purpose of the Study:

• To develop a versatile synthetic route for pyranose-based peptide mimetics.
• To create molecules with substituents held close to the scaffold for defined pharmacophore positioning.
• To generate systematically diverse libraries of monosaccharide-based mimetics.

Main Methods:

• Development of a versatile synthetic route using 2-amino pyranose scaffolds.
• Regio- and stereospecific introduction of various substituent types.
• Solid-phase diversification steps for library generation.
• Application of the method to glucose and allose scaffolds.

Main Results:

• A versatile synthetic route toward peptide mimetics based on 2-amino pyranose scaffolds was established.
• The method allows for a wide range of substituent types with regio- and stereospecificity.
• Systematically diverse libraries of several hundred monosaccharide-based mimetics were produced, positioning three binding elements in various 3D orientations.

Conclusions:

• The developed synthetic strategy provides access to pyranose-based drug-like mimetics with precisely controlled pharmacophore presentation.
• This approach is adaptable to various pyranose building blocks, including glucose and allose.
• The method facilitates the production of diverse chemical libraries for drug discovery efforts.