Mechanistic studies and methods to prevent aglycon transfer of thioglycosides
Mechanistic studies and methods to prevent aglycon transfer of thioglycosides
复制标题
DOI：
10.1021/ja063247q
复制
发表时间：
2006-09-06
影响因子：
15
通讯作者：
Gildersleeve, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Li, Zhitao;Gildersleeve, Jeffrey C.
硫代糖苷已广泛用于合成复杂的寡糖、碳水化合物库和 O-糖苷模拟物。虽然非常有用，但糖苷转移是硫代糖苷的一个有问题的副反应。本文描述了一系列机制研究。糖苷转移过程被证明会影响武装和解除武装的硫糖苷，引起硫糖苷碳硫键的异构化，并破坏糖基化反应的产物。结果表明，苷元转移过程可能是多种硫代糖苷的主要问题。在进行固相糖基化、一锅或正交多组分糖基化以及碳水化合物库构建等复杂反应时，考虑这种副反应尤其重要。为了防止转移，检查了许多修饰的苷元。在各种模型研究和糖基化反应中，发现 2,6-二甲基苯基 (DMP) 苷元可有效阻断转移。 DMP基团可以通过市售硫醇（2,6-二甲基苯硫酚）一步安装，并且可用作糖基供体。基于这些特征，DMP基团被提议作为硫代糖苷类的一种方便且改进的苷元。
Thioglycosides have been employed extensively for the synthesis of complex oligosaccharides, carbohydrate libraries, and mimetics of O-glycosides. While very useful, aglycon transfer is a problematic side reaction with thioglycosides. In this paper, a series of mechanistic studies are described. The aglycon transfer process is shown to affect both armed and disarmed thioglycosides, cause anomerization of the carbon-sulfur bond of a thioglycoside, and destroy the product of a glycosylation reaction. The results indicate that the aglycon transfer process can be a major problem for a wide range of thioglycosides. This side reaction is especially important to consider when carrying out complex reactions such as solid-phase glycosylations, one-pot or orthogonal multicomponent glycosylations, and construction of carbohydrate libraries. To prevent transfer, a number of modified aglycons were examined. The 2,6-dimethylphenyl ( DMP) aglycon was found to effectively block transfer in a variety of model studies and glycosylation reactions. The DMP group can be installed in one step from a commercially available thiol ( 2,6-dimethylthiophenol) and is useable as a glycosyl donor. On the basis of these features, the DMP group is proposed as a convenient and improved aglycon for thioglycosides.