Synthesis of Analogues of Marine Glycosphingolipids

Studying the chemistry of marine sponges of the genus Agelas and Axinella, our research group discovered α- galactosylglycosphingolipids, a new class of glycolipids characterized by the presence of an α-galactopyranose as the first sugar of the saccharide chain. Some of these compounds showed immunostimulating properties, being able to induce proliferation of T cells in vitro, others resulted to be inactive. By a comparison of the structure of active and inactive glycolipids, we proposed a structure-activity relationship for the immunomodulating activity: only glycosphingolipids with a non-glycosylated OH at position 2 of the first sugar are immunostimulating agents. To confirm this hypothesis and to perform more detailed structure-activity studies, we needed a collection ot compounds with a greater structural variety than that provided by natural compounds. Therefore, we decided to synthesize some analogues of natural α-galactosylglycosphingolipids modified at position 2 of the first sugar. We set up an efficient procedure for the synthesis of glycosphingolipids with trihydroxylated sphingosines, that we used for the preparation of analogues. This synthetic study showed some interesting new aspects of carbohydrate chemistry, such as the use of sodium dithionite as an efficient and mild dehalogenating agent.