Immunomodulatory α-galactoglycosphingolipids:: Synthesis of a 2′-O-methyl-α-Gal-GSL and evaluation of its immunostimulating capacity

The total synthesis of 1-2-docosanoylamino-O-(2-O-methyl-alpha-D-galactopyranosyl)-1,3,4-octadecanetriol (2), a 2'-methoxy analog of the immunostimulating alpha-galactoglycosphingolipid 1, is reported. Stereoselective alpha-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 alpha-Gal-GSLs. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).