Direct and stereoselective synthesis of β-linked 2,6-deoxyoligosaccharides
Direct and stereoselective synthesis of β-linked 2,6-deoxyoligosaccharides
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DOI：
10.1002/anie.200604031
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Takahashi, Takashi
中科院分区：
文献类型：
--
作者：
Tanaka, Hiroshi;Yoshizawa, Atsushi;Takahashi, Takashi
2，6-二脱氧糖和2，3，6-三脱氧糖是许多具有生物活性的天然产物的关键组分[1]，并且是困难且具有挑战性的合成目标。[2]在酸性糖基化条件下，糖单元上不存在吸电子取代基容易促进β-糖苷的端基异构化为两种以上的端基异构体。此外，C2位取代基参与相邻基团的不可利用性和由减少的取代基数目产生的增强的构象灵活性使得难以以立体选择性方式实现糖苷化。间接方法涉及使用糖基供体和受体，立体定向和吸电子取代基如卤化物和硫化物在C2位连接到所述糖基供体和受体，已经被开发来克服这些问题。[3]C2位的取代基通过手性效应促进立体选择性糖苷化，并防止所产生的糖苷键在酸性糖苷化条件下发生端基异构化。另一方面，有几种方法可用于直接β-选择性糖基化，其中α-糖基卤化物[4]和糖基亚磷酸酯[5]用作糖基供体。然而，通过直接和立体选择性糖苷化合成β-连接的2，6-二或2，3，6-三脱氧寡糖仍然难以实现。[6]本文中，我们描述了一种基于糖基亚氨酸氧化活化的直接β-选择性糖苷化反应，并报道了其在合成β-连接2-脱氧寡糖中的应用。
2, 6-Di-and 2, 3, 6-trideoxysaccharides are key components of many biologically active natural products [1] and are difficult and challenging synthetic targets.[2] The absence of electronwithdrawing substituents on the saccharide units readily promotes the anomerization of β-glycosides to more than two anomeric isomers under acidic glycosylation conditions. Furthermore, the non-availability of neighboring-group participation from substituents at C2 and the enhanced conformational flexibility derived from the reduced number of substituents make it difficult to achieve glycosidation in a stereoselective manner.Indirect methods involving the use of glycosyl donors and acceptors to which stereodirecting and electron-withdrawing substituents, such as halides and sulfides, are attached at the C2 position, have been developed to overcome these problems.[3] The substituents at C2 promote stereoselective glycosidation through an anchimetric effect and prevent the generated glycosidic linkages from anomerization under the acidic glycosidation conditions. On the other hand, several methods are available for direct β-selective glycosylations, in which α-glycosyl halides [4] and glycosyl phosphites [5] are used as glycosyl donors. However, the synthesis of β-linked 2, 6-dior 2, 3, 6-trideoxyoligosaccharides by direct and stereoselective glycosidation continues to be difficult to accomplish.[6] Herein, we describe a direct β-selective glycosidation based on the oxidative activation of glycosyl imidates and report its application to the synthesis of β-linked 2-deoxyoligosaccharides.