Synthesis of β-1,4-di-d-mannuronic acid glycosides as potential ligands for toll-like receptors

Toll-like receptors (TLRs) play important roles in host immune defense, and synthetic TLR ligands are useful therapeutic agents for a variety of diseases including infection, inflammation, and cancers. Alginates are strong immune stimulants mediated by TLR2/4. Reported here are the design and chemical synthesis of two glycosides (1 and 2) containing β-1,4-di-d-mannuronic acid moiety derived from alginate. The synthesis features the preparation of β-1,4-d-mannobiose derivatives through diastereoselective β-glycosylation of 4,6-di-O-benzylidene protected thiomannoside donor 7, followed by an oxidation step using TEMPO/BAIB to provide the β-1,4-di-d-mannuronic acid moiety.