Regioselective Glycosylation of Non-protected Methyl Hexopyranosides Using the Stannylene Activation Method

由于传统的保护-去保护方法使整个合成方案冗长且不切实际，因此迫切需要开发一种新的无保护糖的区域选择性糖基化方法。化学反应应该更有选择性，更快速，更有效率。在这种情况下，很少有先例表明，未受保护的己核苷的乙烯介导的区域选择性糖基化使得一些低聚糖的一锅组装成为可能。然而，以往的方法仅限于提供α / β-（1→6）键连接的双糖，即糖基化反应优先于己糖的一级羟基，并且糖基化反应的产率并不总是很高。因此，有必要开发一种新的区域选择性糖基化，即使在伯羟基存在的情况下也适用于仲羟基，例如，α / β-（1→3）键双糖。我们开发了一种新的方法，区域和立体选择性糖基化的完全无保护的甲基己核苷的锡炔活化法。Ag(I)-硅铝促进单锅法中锡化糖的糖基化反应主要产β-（1→6）键双糖。此外，在反应介质中加入一些四丁基铵盐，对无保护的甲基β- d -半乳糖苷的糖基化产生了显著的区域选择性改变，使葡萄糖基-β-(1→3)-半乳糖苷优先于相应的β-(1→6)-连接的双糖。由于糖基β-(1→3)-半乳糖苷片段是许多免疫相关低聚糖的核心双糖单元，因此本文报道的方法将有助于合成碳水化合物化学，这可以替代传统的“保护-去保护”方法。

Developing a new method for regioselective glycosylation of unprotected sugars is highly desired, since the conventional protection-deprotection method renders the overall synthetic scheme lengthy and impractical. Chemical reactions should be much more selective, rapid, and productive.In this context, very few precedents have revealed that the stannylene-mediated regioselective glycosylation of unprotected hexopyranosides makes it possible to provide one-pot assembly of some oligosaccharides. However, the previous methods were limited to afford α / β-(1 → 6)-linked disaccharides only, I.e., glycosylation of the primary hydroxyl group of hexoses is preferred, and the yields of the glycosylation reaction are not always high. Therefore, it is necessary to develop a novel regioselective glycosylation applicable to the secondary hydroxyl groups even in the presence of the primary hydroxyl one, giving for example, α / β-(1→3)-linked disaccharides.We have developed a novel methodology of regio- and stereoselective glycosylation for fully unprotected methyl hexopyranosides by the stannylene activation method. Ag(I)-silica alumina-promoted glycosylation of stannylated sugars in the one-pot process was shown to yield β-(1 → 6)-linked disaccharides predominantly. Furthermore, addition of some tetra butylammonium salts to the reaction medium provides a significant regioselectivity shift on the glycosylation of unprotected methyl β-D-galactopyranoside, affording glucosyl-β-(1 → 3) -galactoside in preference to the corresponding β-(1→6)-linked disaccharide.Since glycosyl β-(1→ 3)-galactoside moiety is well known as a core disaccharide unit of many immunologically relevant oligosaccharides, the method reported here would contribute to synthetic carbohydrate chemistry, which can be an alternative to the conventional "protection-deprotection" method.