Synthesis and biological activities of glycosphingolipid analogues from marine sponge Aplysinella rhax

A novel glycosphingolipid analogue β- d-GalNAc p(1-4)[α- d-Fuc p(1-3)]-β- d-GlcNAc p(1-R) ( 2) and some non-natural type trisaccharide analogues were synthesized, and their ability to inhibit the nitric oxide release was also examined. A novel glycosphingolipid, β- d-GalNAc p(1 → 4)[α- d- Fuc p(1 → 3)]-β- d-GlcNAc p(1→)Cer ( 1), isolated from the marine sponge Aplysinella rhax, has a unique structure, with d-fucose and N-acetyl- d-galactosamine attached to a reducing-end N-acetyl- d-glucosamine through an α1 → 3 and β1 → 4 linkage, respectively. We synthesized glycolipid analogues carrying a 2-branched fatty alkyl residue or a 2-trimethylsilyl ethyl residue in place of ceramide ( 2 and 3), non-natural type trisaccharide analogue containing an l-fucose residue ( 4), and other analogues ( 5 and 6). Among these prepared compounds, 2 showed the most potent nitric oxide (NO) production inhibitory activity against LPS-activated J774.1 cells. In addition, their structure–activity relationships were established.