A general strategy for stereoselective glycosylations
A general strategy for stereoselective glycosylations
复制标题
DOI：
10.1021/ja052548h
复制
发表时间：
2005-08-31
影响因子：
15
通讯作者：
Boons, GJ
中科院分区：
文献类型：
--
作者：
Kim, JH;Yang, H;Boons, GJ
具有生物重要性的寡糖的合成所面临的主要挑战是开发用于立体选择性引入糖苷键的通用方法。本文表明，糖基供体的C-2处的（1 S）-苯基-2-（苯硫基）乙基部分可以进行相邻基团参与，得到准稳定的异头锍离子。由于空间和电子因素，形成的硫离子作为陷阱-十氢萘环系统。通过羟基置换锍离子导致立体选择性地形成α-糖苷。采用NMR实验来令人信服地显示β-连接的锍离子中间体的存在。（1 S）-苯基-2-（苯硫基）乙基部分可以通过糖醇与乙酸（1 S）-苯基-2-（苯硫基）乙酯在BF 3-OEt 2存在下反应来引入。此外，它可以通过在乙酸酐中用BF 3-OEt 2处理转化为乙酸酯而除去。引入以及裂解反应通过中间体表锍离子的形成而进行。使用新的方法结合传统的相邻基团参与酯引入β-糖苷，使得有可能，第一次，合成各种各样的低聚糖的常规程序。后者通过Galili三糖的合成来证明，Galili三糖已被鉴定为可以通过一锅两步糖基化序列在异种移植中引发急性排斥的表位。
The principal challenge that the synthesis of oligosaccharides of biological importance presents is the development of a general approach for the stereoselective introduction of a glycosidic linkage. It is shown here that a (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety at C-2 of a glycosyl donor can perform neighboring group participation to give a quasi-stable anomeric sulfonium ion. Due to steric and electronic factors, the sulfonium ion is formed as a traps-decalin ring system. Displacement of the sulfonium ion by a hydroxyl leads to the stereoselective formation of alpha-glycosides. NMR experiments were employed to show convincingly the presence of the beta-linked sulfonium ion intermediate. The (1 S)-phenyl-2-(phenylsulfanyl)ethyl moiety could be introduced by reaction of a sugar alcohol with acetic acid (1 S)-phenyl-2(phenylsulfanyl)ethyl ester in the presence of BF3-OEt2. Furthermore, it could be removed by conversion into acetate by treatment with BF3-OEt2 in acetic anhydride. The introduction as well as the cleavage reaction proceeds through the formation of an intermediate episulfonium ion. The use of the new methodology in combination with traditional neighboring group participation by esters to introduce beta-glycosides makes it possible, for the first time, to synthesize a wide variety of oligosaccharides by routine procedures. The latter was demonstrated by the synthesis of the Galili trisaccharide, which has been identified as an epitope that can trigger acute rejections in xeno-transplantations, by the one-pot two-step glycosylation sequence.