SYNTHESIS OF THE THIO-LINKED GANGLIOSIDE GM(3) EPITOPE

The synthesis of sulfur-linked GM(3) epitope 2 is based on acid-cataly zed and base-promoted S-glycosylation processes. As a precursor, 2-O-b enzoyl-3-thiogalactoside 10 was required, and was obtained from 4,6- O -benzylidene-galactoside 3 in six high-yielding steps. Base-promoted S -glycosylattion of 10 with neuraminic acid functionalized beta-halogen ose 11 in the presence of NaH as base and Kryptofix 21 as coactivator afforded alpha(2-3)-thio-linked disaccharide 13, which was readily con verted to alpha-halogenose 20. Heptyl 1-thioglycoside 22 was obtained from O-galactosyl trichloroacetimidate 21 and heptylthiol via acid-cat alyzed S-glycosylation. 22 was transformed into 2,3,6-tri-O-aoilgalact oside 26 which, via the 4-O-triflate and treatment with potassium thio acetate, followed by selective removal of the S-acetyl group, furnishe d the 2,3,6-tri-0-acyl-4-thioglucoside 28. Base-promoted S-glycosylati on of 28 with halogenose 20 led to fully acylated target molecule 29, which was quantitatively converted into 2.