Polymer-Supported Synthesis of Oligosaccharides Using a Diisopropylsiloxane Linker and Trichloroacetimidate Donors

We describe herein the polymer-supported synthesis of biologically relevant oligosaccharides using a diisopropylsiloxane linker and trichloroacetimidates as glycosyl donors. Siloxane linkers offer important advantages over closely related silyl ethers since even sterically hindered alcohols can be directly loaded onto commercially available polymers, such as soluble polyethylene glycol (PEG), without prior manipulation of the support. Final products can be easily detached by mild fluoridolysis to afford OH-tagged sugar probes. We followed an acceptor-bound approach that fixed the nucleophile on the polymer, and we selected soluble PEG as the support due to higher reactivity of bound sugars and easy reaction monitoring. Following this strategy, the trisaccharide repeating unit of the capsular polysaccharide of Neisseria meningitidis (serogroup L) and the disaccharide containing the structural motif of hyaluronic acid were successfully synthesized.