Immunomodulatory a-galactosyl glycosphingolipids : synthesis of a 2'-O-methyl- a -galactosyl-GSL and evaluation of its immunostimulating capacity

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.