Synthesis of β-(1→4)-oligo-D-mannuronic acid neoglycolipids

Mammalian Toll-like receptors (TLRs) play important roles in host immune defense. The activation of TLR and downstream signaling pathways have great impact on human physiology. Chemically diverse microbial products as well as synthetic ligands serve as agonists for these receptors. Recently, synthetic TLR ligands are being exploited as useful therapeutic agents for a variety of diseases including infections, inflammatory diseases, and cancers. Alginate polymers and oligosaccharides are strong immune stimulants mediated by TLR2/4, but synthesis of alginate oligomers is rarely studied. Reported here are the design and chemical synthesis of two beta-(1 -> 4)-di- and beta-(1 -> 4)-tri-D-mannuronic acid neoglycolipids 1 and 2 as potential TLR ligands. By using 4,6-di-O-benzylidene-protected 1-thio mannoside 7 as a glycosyl donor, the diastereoselective beta-D-mannosylation protocol provides the beta-(1 -> 4)-D-mannobiose and beta-(1 -> 4)-D-mannotriose derivatives, which upon regioselective oxidation with TEMPO/BAIB oxidation system yield the corresponding beta-(1 -> 4)-D-mannuronic acid containing neoglycolipids 1 and 2. (c) 2007 Elsevier Ltd. All rights reserved.