Kovác P, Lerner L
National Institutes of Health, Bethesda, Maryland 20892.
Carbohydr Res. 1988 Dec 31;184:87-112. doi: 10.1016/0008-6215(88)80008-9.
Acid-catalyzed thiophenolysis of 1,6-anhydro-2,3,4-tri-O-benzyl-beta-D-glucopyranose and acetylation of the resulting phenyl 2,3,4-tri-O-benzyl-1-thio-alpha-D-glucopyranoside (4) gave phenyl 6-O-acetyl-2,3,4-tri-O-benzyl-1-thio-alpha-D-glucopyranoside (5). Reaction of 5 with chlorine gave, stereospecifically, the corresponding beta-glycosyl chloride, which was treated with 4 in the presence of silver perchlorate and 2,4,6-trimethylpyridine to afford phenyl O-(6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-glucopyranosyl)-(1----6)-2,3,4- tri-O- benzyl-1-thio-alpha-D-glucopyranoside (17). Crystalline O-(6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-glucopyranosyl)-(1----6)-2,3,4- tri- O-benzyl-beta-D-glucopyranosyl chloride, readily obtainable in a stereo-specific manner from 17 by treatment with chlorine, was used as the key glycosyl (isomaltosyl) donor in the blockwise synthesis of methyl glycosides of isomalto-oligosaccharides, up to and including the octasaccharide. The methyl alpha-glycoside of isomaltotetraose fluorinated at C-6 of the terminal D-glucopyranosyl group was prepared by using SnCl2-activated 2,3,4-tri-O-benzyl-6-deoxy-6-fluoro-alpha,beta-D-glucopyranosyl fluoride as the glycosyl donor, a suitably protected methyl alpha-isomaltotrioside as the nucleophile, and silver perchlorate as the promoter. The n.m.r. spectra (1H- and 13C-) of numerous synthetic intermediates were analyzed and completely assigned by a variety of two-dimensional homo- and hetero-nuclear n.m.r.-spectroscopic techniques, and the final deprotected title oligosaccharides were characterized by 13C-n.m.r. data. Silver perchlorate-mediated glycosylation reactions involving beta-glycosyl chlorides were high-yielding and showed high stereo-selectivity for the formation of an alpha-(cis)-glycosidic linkage. The practical limitation of obtaining high isomalto-oligosaccharides in this way appears to lie solely in the separation technique applied for the resolution of the crude products formed.
1,6 - 脱水 - 2,3,4 - 三 - O - 苄基 - β - D - 吡喃葡萄糖的酸催化硫代苯解反应以及所得苯基2,3,4 - 三 - O - 苄基 - 1 - 硫代 - α - D - 吡喃葡萄糖苷（4）的乙酰化反应得到苯基6 - O - 乙酰基 - 2,3,4 - 三 - O - 苄基 - 1 - 硫代 - α - D - 吡喃葡萄糖苷（5）。5与氯反应，立体专一性地得到相应的β - 糖基氯，其在高氯酸银和2,4,6 - 三甲基吡啶存在下与4反应，得到苯基O - （6 - O - 乙酰基 - 2,3,4 - 三 - O - 苄基 - α - D - 吡喃葡萄糖基） - （1→6） - 2,3,4 - 三 - O - 苄基 - 1 - 硫代 - α - D - 吡喃葡萄糖苷（17）。通过用氯处理17以立体专一的方式容易获得的结晶状O - （6 - O - 乙酰基 - 2,3,4 - 三 - O - 苄基 - α - D - 吡喃葡萄糖基） - （1→6） - 2,3,4 - 三 - O - 苄基 - β - D - 吡喃葡萄糖基氯，被用作异麦芽糖低聚糖甲基糖苷逐步合成中直至包括八糖的关键糖基（异麦芽糖基）供体。通过使用SnCl₂活化的2,3,4 - 三 - O - 苄基 - 6 - 脱氧 - 6 - 氟 - α,β - D - 吡喃葡萄糖基氟作为糖基供体、适当保护的甲基α - 异麦芽三糖苷作为亲核试剂以及高氯酸银作为促进剂，制备了在末端D - 吡喃葡萄糖基的C - 6位氟化的异麦芽四糖甲基α - 糖苷。通过各种二维同核和异核核磁共振光谱技术对众多合成中间体的核磁共振谱（¹H - 和¹³C - ）进行了分析并完全归属，最终脱保护的目标低聚糖通过¹³C - 核磁共振数据进行了表征。涉及β - 糖基氯的高氯酸银介导的糖基化反应产率高，并且对α - （顺式）糖苷键的形成显示出高立体选择性。以这种方式获得高异麦芽糖低聚糖的实际限制似乎仅在于用于分离所形成粗产物的分离技术。
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