Kameyama A, Ishida H, Kiso M, Hasegawa A
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Carbohydr Res. 1990 Apr 25;200:269-85. doi: 10.1016/0008-6215(90)84197-3.
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.
本文描述了唾液酸乳糖四糖神经酰胺（28，IV3NeuAcLc4Cer）和唾液酸新乳糖四糖神经酰胺（32，IV3NeuAcnLc4Cer）的首次全合成。关键糖基供体O-（甲基5-乙酰氨基-4,7,8,9-四-O-乙酰基-3,5-二脱氧-D-甘油-α-D-半乳糖-2-壬酮吡喃糖醛酸酯）-（2→3）-2,4,6-三-O-苯甲酰基-1-硫代-β-D-吡喃半乳糖苷（4）由2-（三甲基硅基）乙基O-（甲基5-乙酰氨基-4,7,8,9-四-O-乙酰基-3,5-二脱氧-D-甘油-α-D-半乳糖-2-壬酮吡喃糖醛酸酯）-（2→3）-6-O-苯甲酰基-β-D-吡喃半乳糖苷（1）经苯甲酰化、用乙酰基取代2-（三甲基硅基）乙基、并用甲硫基三甲基硅烷引入甲硫基制备而成。由2-（三甲基硅基）乙基β-D-乳糖苷（5）经选择性3'-O-（4-甲氧基苄基化）、苄基化以及选择性除去4-甲氧基苄基制备得到的2-（三甲基硅基）乙基2,3,6,二-O-苄基-β-D-乳糖苷（8），与3,4,6-三-O-乙酰基-2-脱氧-2-邻苯二甲酰亚氨基-D-吡喃葡萄糖基溴（9）偶联得到三糖衍生物10，然后除去邻苯二甲酰基和O-乙酰基。接着进行N-乙酰化得到2-（三甲基硅基）乙基O-（2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基）-（1→3）-O-（2,4,6-三-O-苄基-β-D-吡喃半乳糖基）-（1→4）-2,3,6-三-O-苄基-β-D-吡喃葡萄糖苷（12）。用三氟甲磺酸二甲硫鎓盐促进4与由12经4,6-O-亚苄基化制备得到的13或与由13经O-（4-甲氧基苄基化）和亚苄基缩醛的还原开环得到的15偶联，以良好产率得到相应的五糖衍生物16和20。化合物16和20转化为相应的α-三氯乙亚胺酯19和23，它们与（2S,3R,4E）-2-叠氮基-3-O-苯甲酰基-4-十八碳烯-1,3-二醇（24）偶联，分别得到β-糖苷25和29。最后，25和29分别经叠氮基的选择性还原、与十八烷酸缩合、O-脱酰基以及甲酯基水解转化为28和32。
