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 (I and 2) containing beta-1,4-di-D-mannuronic acid moiety derived from alginate. The synthesis features the preparation of beta-1,4-D-mannobiose derivatives through diastereoselective P-glycosylation of 4,6-di-O-benzylidene protected thiomannoside donor 7, followed by an oxidation step using TEMPO/BAIB to provide the beta-1,4-di-D-mannuronic acid moiety. (c) 2007 Elsevier Ltd. All rights reserved.