An efficient synthesis of ganglioside GM3 : highly stereocontrolled glycosylations by use of auxiliaries

An efficiently stereocontrolled total synthesis of GM3 alpha-D-Neup5Ac-(2---3)-beta-D-Galp-(1---4)-beta-D-Glcp-(1---1) -Cer was achieved by employing both methyl 5-acetamido-4,7,8,9-tetra-O-benzyl-2-bromo-2,3,5-trideoxy-3- phenylthio-D-erythro-beta-L-gluco-2-nonulopyranosonate for the key sialylation step, and O-[methyl(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha -D-galacto-2-nonulopyranosyl)onate]-(2---3)-O-(2,4,6-tri-O- acetyl-beta-D-galactopyranosyl-(1---4)-3,6-di-O-acetyl-2-O-pivaloyl- alpha-D-glucopyranosyl trichloroacetimidate and fluoride for the key coupling step with a ceramide derivative. These two steps were significantly altered and improved in comparison with our previous synthesis that had been executed without use of stereocontrolling auxiliaries. GM3 was obtained in 4.5% overall yield in 19 steps starting from allyl O-(2,6-di-O-acetyl-3,4-O-isopropylidene-beta-D-galactopyranosyl)-(1---4 )-2,3,6-tri-O-acetyl-beta-D-glucopyranoside.