Simplexide revisited, and other glycolipid stories

In the last ten years, glycolipids for marine organisms (sponges in particular) have been shown to be an exceptionally rich source of chemical diversity. These compounds often show peculiar biological activities and, for example, agelasphin, an alpha-galactosylceramide first isolated form the sponge Agelas mauritiana, is the reference ligand for the CD1d protein, an antigen presenting molecule which binds and presents glycolipids to T lymphocytes. The most recent contributions in this field from our group will be presented.Simplexide (1), glycoside of a very-long-chain secondary alcohol, has been isolated sever years ago from the Caribbean sponges Plakortis simplex. We have now completed the total synthesis of simplexide, and shown that it is a potent stimulus for endogenous IL-10 production by Peripheral Blood Mononuclear Cells (PBMC), and more generally induces a unique profile of cytokine release. Vesparioside B (2) is a new glycosphingolipid isolated from the sponge Spheciospongia vesparia, characterized by a complex hexasaccharide chain with three sugars in the furanose form. Its structure elucidation led to establish a new method to correlate the relative configuration of the ring carbons to vicinal proton-proton coupling constant values in the five-membered furanose sugar. The same method was then used for the structure elucidation of another complex glycosphingolipid from a Terpios sponge.