Acceptor-Adaptive Automated Glycosylation Optimization for Automated Glycan Assembly

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Process Optimization

Background:

• Automated solid-phase glycan assembly requires precise temperature control for efficiency.
• Evaluating glycosyl acceptors' impact on glycosylation efficiency (GE) is challenging.
• Simple alkyl acceptors offer limited relevance for optimization.

Purpose of the Study:

• To develop a reliable system for optimizing glycosylation temperatures in automated solid-phase glycan assembly.
• To identify a glycosyl acceptor that accurately reflects optimal reaction conditions for diverse acceptors.
• To improve atom economy and energy efficiency in carbohydrate synthesis.

Main Methods:

• Developed and validated a modified trans-4-aminocyclohexanol-based acceptor for temperature optimization.
• Compared optimization results using the modified acceptor with various other glycosyl acceptors.
• Applied optimized temperatures to automated solid-phase synthesis (SPS) of disaccharides.

Main Results:

• The modified acceptor accurately predicted optimal glycosylation temperatures for multiple glycosyl acceptors.
• This approach overcame the limitations of using simple alkyl acceptors or impractical screening.
• Optimized temperatures led to highly efficient SPS of disaccharides.

Conclusions:

• A modified trans-4-aminocyclohexanol-based acceptor serves as a reliable proxy for optimizing glycosylation temperatures.
• This method enhances the efficiency and practicality of automated solid-phase glycan assembly.
• The findings facilitate the development of more energy-efficient and atom-economical carbohydrate synthesis processes.