Department of Chemistry, University of California at Davis , One Shields Avenue, Davis, California 95616, United States.
J Org Chem. 2013 Oct 4;78(19):9677-88. doi: 10.1021/jo4013805. Epub 2013 Sep 17.
Glycoconjugates are composed of carbohydrate building blocks linked together in a multitude of ways giving rise to diverse biological functions. Carbohydrates are especially difficult to synthetically manipulate because of the similar reactivity of their numerous and largely equivalent hydroxyl groups. Hence, methodologies for both the efficient protection and selective modification of carbohydrate alcohols are considered important synthetic tools in organic chemistry. When per-O-TMS protected mono- or disaccharides in a mixture of pyridine and acetic anhydride are treated with acetic acid, regioselective exchange of silicon for acetate protecting groups occurs. Acid concentration, thermal conditions, and microwave assistance mediate the silyl/acetate exchange reaction. Regiocontrol is achieved by limiting the equivalents of acetic acid, and microwave irradiation hastens the process. We coined the term Regioselective Silyl Exchange Technology (ReSET) to describe this process, which essentially sets the protecting groups anew. To demonstrate the scope of the reaction, the conditions were applied to lactose, melibiose, cellobiose, and trehalose. ReSET provided rapid access to a wide range of orthogonally protected disaccharides that would otherwise require multiple synthetic steps to acquire. The resulting bifunctional molecules are poised to serve as modular building blocks for more complex glycoconjugates.
糖缀合物由碳水化合物结构单元以多种方式连接而成，具有多种生物功能。由于其大量且大部分等效的羟基具有相似的反应性，因此碳水化合物特别难以进行合成操作。因此，高效保护和选择性修饰碳水化合物醇的方法被认为是有机化学中的重要合成工具。当在吡啶和乙酸酐的混合物中用乙酸处理全-O-TMS 保护的单糖或二糖时，硅对乙酸酯保护基的区域选择性交换会发生。酸浓度、热条件和微波辅助调节硅烷/乙酸酯交换反应。通过限制乙酸的当量来实现区域控制，并且微波辐射会加快该过程。我们创造了术语“区域选择性硅烷交换技术（ReSET）”来描述该过程，该过程实质上是重新设置保护基团。为了证明反应的范围，将条件应用于乳糖、蜜二糖、纤维二糖和海藻糖。ReSET 快速获得了广泛的正交保护的二糖，否则需要多个合成步骤才能获得。所得的双功能分子有望成为更复杂的糖缀合物的模块化构建块。
