Stereoselective synthesis of sialyl-lactotetraosylceramide and sialylneolactotetraosylceramide.
The first total syntheses of sialyl-lactotetraosylceramide (28, IV3NeuAcLc4Cer) and sialylneolactotetraosylceramide (32, IV3NeuAcnLc4Cer) are described. Methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero- alpha-D-galacto-2-nonulopyranosylonate)-(2----3)-2,4,6-tri-O-benzo yl-1-thio- beta-D-galactopyranoside (4), the key glycosyl donor, was prepared from 2-(trimethylsilyl)ethyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosylonate)-(2----3)-6-O-benzoyl-beta-D-galactopyranosid e (1), via benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group with methylthiotrimethylsilane. Coupling of 2-(trimethylsilyl) ethyl 2,3,6,2',4',6'-hexa-O-benzyl-beta-D-lactoside (8), prepared from 2-(trimethylsilyl)ethyl beta-D-lactoside (5) via selective 3'-O-(4-methoxybenzylation), benzylation, and selective removal of the 4-methoxybenzyl group, with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide (9) gave a trisaccharide derivative 10, from which the phthaloyl and O-acetyl groups were removed. N-Acetylation then gave 2-(trimethylsilyl)ethyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-(2,4,6-tri-O-be nzyl- beta-D-galactopyranosyl)-(1----4)-2,3,6-tri-O-benzyl-beta-D-glucopyranos ide (12). Dimethyl(methylthio)sulfonium triflate-promoted coupling of 4 with 13, prepared from 12 by 4,6-O-benzylidenation, or with 15, obtained from 13 by O-(4-methoxybenzylation) and reductive opening of the benzylidene acetal, gave the corresponding pentasaccharide derivatives 16 and 20 in good yields. Compounds 16 and 20 were converted into the corresponding alpha-trichloroacetimidates 19 and 23 which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (24), gave the beta-glycosides 25 and 29, respectively. Finally, 25 and 29 were transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into 28 and 32, respectively.
Kameyama
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Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Ishida
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H
Kiso
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Hasegawa
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A
D002240:Carbohydrate Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D005732:Gangliosides / Q000138:chemical synthesis*; D005915:Globosides / Q000138:chemical synthesis*; D006028:Glycosphingolipids / Q000138:chemical synthesis*; D006031:Glycosylation; D008969:Molecular Sequence Data; D013237:Stereoisomerism
D005732:Gangliosides; D005915:Globosides; D006028:Glycosphingolipids; C000592361:sialyl-lactotetraosylceramide; C037790:sialosylgloboside; C056352:2-3-N-acetylneuraminyl-1-3-galactosyl-1-3-N-acetylglucosyl-1-4-galactosyl-1-glucosylceramide