Immunomodulatory α-Galactosyl Glycosphingolipids: Synthesis of a 2'-O-Methyl-α-Galactosyl-GSL and Evaluation of its Immunostimulating Capacity

The total synthesis of 1-2-docosanoylamino-O-(2-O-methyl-α-D-galactopyranosyl)-1,3,4-octadecanetriol (2), a 2-methoxy analog of the immunostimulating α-galactoglycosphingolipid 1, is reported. Stereoselective α-glycosylation of the azido precursor of sphingosine was successfully performed for the first time using an improved Mukaiyama reaction. When assayed in a 72 h splenocyte proliferation test, compound 2 was significantly less stimulatory than the non-methylated compound 1, suggesting that the galactose 2-OH group is essential for the immunostimulatory activity of α-Gal-GSLs.