Stereoselective synthesis of a 2-deoxyglycosphingolipid

Studying the chemistry of marine sponges of the genus Agelas and Axinella, our research group discovered alpha-galactosylglycosphingolipids, a new class of glycolipids characterized by the presence of an alpha-galactopyranose as the first sugar of the saccharide chain.1 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.2 In order to perform more detailed structure-activity studies, we decided to synthesize some analogues of natural -galactosylglycosphingolipids modified at position 2 of the first sugar. Our first target was 1-O-(2-deoxy--D-galactopyranosyl)-2-docosanoylamino-1,3,4-octadecanetriol (1). This communication describes a stereoselective and efficient strategy to the total synthesis of 2-deoxy--glycosylceramides, using galactal as chiral starting material for both the sphingosine and the sugar units. In addition, this synthetic work led to the discover of some interesting new aspects of carbohydrate chemistry, that will also be discussed.