Acceptor-Adaptive Automated Glycosylation Optimization for Automated Glycan Assembly.

Optimization of glycosylation temperatures is essential for automated solid-phase glycan assembly. Constructing a reliable optimization system that mimics key reaction components is crucial for increasing the atom economy and the energy efficiency of the process. Although glycosyl acceptors play a pivotal role in glycosylation, evaluating their effect on glycosylation efficiency (GE) is nontrivial. While screening various glycosyl acceptors for optimization is impractical, compromising for simple alkyl acceptors produces results of dubious relevance. We demonstrate that optimization with a modified trans-4-aminocyclohexanol-based acceptor accurately reflects the optimal glycosylation temperature of several glycosyl acceptors, overcoming previous limitations. The contextual use of both n-alkyl and glycan-mimetic acceptors for automated optimization enabled translation of optimized glycosylation temperature to highly efficient solid-phase synthesis (SPS) of disaccharides.