Immunomodulatory α-galactoglycosphingolipids:: Synthesis of 2′-fluoro-2′-deoxy-α-galactosylceramide and an evaluation of its immunostimulating properties

In the framework of a project to assess the immunomodulating properties of a-galactosyl glycosphingolipids, the total synthesis of 1-O-(2-fluoro-2-deOXy-alpha-D-galactopyranosyl)-2docosanoylamino-1,3,4-octadecanetrioI (1), a 2'-fluoro analogue of the immunostimulating alpha-galactoglycosphingolipids, was accomplished. The glycosidation reaction of the azido precursor of sphingosine was performed using the Mu-kaiyama glycosidation reaction. The stimulation of mouse splenocyte proliferation by the 2'-fluoro analogue was highly reduced compared to that of the a-galactoglycosphingolipids, thereby confirming that a free galactose 2-OH group is essential for the immunostimulatory activity. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).