Synthesis of Glycolipids. 3. Immunomodulatory α-galactoglycolsphingolipids: synthesis of 2'-fluoro-2'-deoxy-α-galactosylceramide and evaluation of its immunostimulating properties

In the framework of a project to assess the immunomodulating properties of α-galactosyl glycosphingolipids, the total synthesis of 1-O-(2-fluoro-2-deoxy-α-D-galactopyranosyl)-2- docosanoylamino-1,3,4-octadecanetriol (1), a 2-fluoro analogue of the immunostimulating α-galactoglycosphingolipids, was accomplished. The glycosidation reaction of the azido precursor of sphingosine was performed using the Mukaiyama glycosidation reaction. The stimulation of mouse splenocyte proliferation by the 2-fluoro analogue was highly reduced compared to that of the α-galactoglycosphingolipids, thereby confirming that a free galactose 2-OH group is essential for the immunostimulatory activity.