Synthetic Studies on Sialoglycoconjugates 74: Synthesis of KDN-gangliosides GM1, GM2, and GD1a

Abstract

Abstract KDN-containing gangliosides GM1, GM2, and GD1a have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-O-(2,6-di-O-benzyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (3) with methyl 6-O-benzyl-2-deoxy-3,4-O-isopropylidene-2-phthalimido-1-thio-β-d-galactopyranoside (5) gave the tetrasaccharide (6), which was converted, via de-esterification, removal of the phthaloyl group, N-acetylation, and O-deisopropylidenation, into the tetrasaccharide acceptor (9). Reductive removal of the benzyl groups in 9, O-acetylation and subsequent removal of the 2-(trimethylsilyl)ethyl group followed by imidate formation, gave the KDN-GM2 oligosaccharide glycosyl donor 12. Glycosylation of 9 with methyl 2,4,6-tri-O-benzoyl-3-O-benzyl-1-thio-β-d-galactopyranoside (13) and methyl (methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-d-glcero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (18), using dimethyl(methyl-thio)sulfonium triflate (DMTST), gave the penta- and hexasaccharides 14 and 19, which were converted via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the corresponding α-trichloroacetimidates 17 and 22. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 12, 17, and 22 in the presence of boron trifluoride etherate afforded the expected β-glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and de-esterification, into the target gangliosides 26 29, and 32.