Oligosaccharide solid-phase synthesis deprotection

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

Advances in solid-phase oligosaccharide synthesis led to the development of an automated platform that was first demonstrated by Peter Seeberger and coworkers in 2001 using a modified peptide synthesizer [38], Automated washing, deprotection, and glycosylation steps dramatically reduced the time and labor usually attributed to solution- and solid-phase synthesis of oligosaccharides. 

Solution-phase oligosaccharide synthesis remains a slow process due to the need for iterative coupling and deprotection steps, with purification at each step along the way. To alleviate the need for repetitive purification events, solid-phase techniques have been developed.29,30 In solid-phase... 

Our approach to oligosaccharide synthesis relied on the acceptor-bound solid-phase method. This method formally reduces the synthesis of carbohydrates to a repetitive cycle of glycosylation and deprotection events. It was reasoned that the repetitive nature of an acceptor-bound glycosylation method rendered it ideal for automation. Therefore, we set out to investigate the potential variables in such a scheme. 

First, a peptide synthesizer was modified to allow solid-phase oligosaccharide synthesis. This platform had the basic function of an automated synthesizer and allowed repeating cycles of glycosylation and deprotection to be mostly software controlled (Fig. 7.2a) [38], This robust pressure-driven system relies on an established... 

---