Solution-phase library synthesis of furanoses.

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Medicinal Chemistry

Background:

• Furanose derivatives are important scaffolds in medicinal chemistry.
• Efficient synthesis of functionalized furanoses is crucial for drug discovery.
• Existing synthetic routes may lack versatility or scalability.

Purpose of the Study:

• To develop a versatile solution-phase synthesis for amido-, urea-, and aminofuranoses.
• To explore the use of reductive amination and acylation for furanose functionalization.
• To demonstrate the utility of scavenger resins in library synthesis of these compounds.

Main Methods:

• Reductive amination of alkylated furanose aldehydes with primary and secondary amines using sodium triacetoxyborohydride.
• Acylation of resulting secondary amines with acid chlorides and isocyanates.
• Acid-catalyzed acetal exchange reactions with alcohols.
• Purification of intermediates and products using functionalized scavenger resins.

Main Results:

• Successful synthesis of secondary and tertiary aminofuranoses.
• Formation of amidofuranoses and ureafuranoses via acylation.
• Preparation of mixed acetals from furanose acetonides.
• Demonstrated efficiency of scavenger resins for purification in library synthesis.

Conclusions:

• A robust and adaptable method for synthesizing diverse amido-, urea-, and aminofuranose libraries has been established.
• The synthetic strategy allows for controlled introduction of various functional groups onto the furanose core.
• The use of scavenger resins streamlines purification, facilitating high-throughput synthesis.