Catalytic Stereoselective Synthesis of Glycosides

人类使用的疫苗和抗凝血剂的发展以及最近糖蛋白的化学合成都突出了碳水化合物合成的力量。因此，方便的化学方法来简化这些复杂分子的合成不仅是合成化学的重要发展，也是糖生物学研究的重要发展，对糖医学领域具有长远的影响。糖苷的立体选择性合成是低聚糖合成的最大挑战之一。复杂碳水化合物的化学合成通常涉及一个完全保护的糖基供体与一个适当保护的含亲核试剂（R-OH）的糖基受体的偶联。在大多数情况下，这些反应会生成两种立体异构体的混合物。立体选择性糖基化最可靠的方法是基于邻基参与（NGP），这需要在C-2位置引入特定的基团来指导亲核攻击。然而，NGP基团的掺入往往是麻烦的，不切实际的，并不是适用于所有类型的单糖，如n - 2,2 -脱氧糖苷等。我们的团队最近报道了一种温和的有机催化方法，用于合成2-脱氧半乳糖苷，具有优异的收率和α选择性。(Angew。化学。Int。编辑（2012），51,36,9152-9155)。本项目旨在发展立体选择性合成糖苷的一般方法和催化方法。

The power of carbohydrate synthesis has been highlighted by the development of vaccines and anticoagulants for human use and the recent chemical synthesis of glycoproteins. Thus, expedient chemical methods to streamline the synthesis of these complex molecules will be an important development not only in synthetic chemistry but also in glycobiology research, with long term impact in the area of glycomedicine. The stereoselective synthesis of glycosides is one of the biggest challenges in oligosaccharide synthesis. The chemical synthesis of complex carbohydrates generally involves the coupling of a fully protected glycosyl donor bearing a leaving group at its anomeric centre with a suitably protected glycosyl acceptor containing a nucleophile (R-OH). In most instances, these reactions lead to a mixture of two stereoisomers. The most reliable method for stereoselective glycosylations is based on neighbouring group participation (NGP), which requires the introduction of specific groups at the C-2 position to direct nucleophilic attack. However, the incorporation of NGP groups is often troublesome, impractical and not applicable to every type of monosaccharide i.e. N-2, 2-deoxy glycosides, etc. Our team have recently reported a mild organocatalytic method for the synthesis of 2-deoxygalactosides, with excellent yields and alpha-selectivity. (Angew. Chem. Int. Ed. (2012), 51, 36, 9152-9155). The proposed project aims to develop general and catalytic methods for the stereoselective synthesis of glycosides.