Synthesis of sphinganine-containing alpha-galactosylceramides

Glycosphingolipids are biologically important molecules located in the external surface of eukaryotic cells. They have been shown to have antitumor and immunostimulatory activity. In order to further understand the interesting biological activities exhibited by glycosphingolipids, effective strategies for their synthesis are critical. ^ The preparation of aminotriol sphingoid bases (phytosphingosines) which form the backbone of many glycosphingolipids is not trivial. Therefore, a straightforward and efficient methodology for the synthesis of aminodiol sphingoid bases (sphinganines) utilizing a serine derived Weinreb amide is presented. Conversion of several sphinganines to glycosphingolipids for evaluation of their biological activities by our collaborators is described. If the sphinganine-containing glycosphingolipids mirrored the potency seen in phytosphingosine-containing glycosphingolipids, structure activity studies would be facilitated. Two sphinganine-containing glycosphingolipids prepared, were found to elicit key cytokines at levels similar to the corresponding phytosphingosine-containing glycosphingolipids.