Catalytic Stereoselective Synthesis of Glycosides

糖苷的催化立体选择性合成

• 批准号: EP/L001926/1
• 负责人: M. Carmen Galan
• 金额: $ 30.79万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL001926%2F1
• 关键词: Catalytic; Stereoselective; Synthesis; Glycosides

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.

碳水化合物合成的力量已经通过疫苗和人用抗凝剂的开发以及最近糖蛋白的化学合成而突出。因此，简化这些复杂分子的合成的便利化学方法不仅在合成化学中而且在糖生物学研究中将是重要的发展，在糖霉素领域具有长期影响。糖苷的立体选择性合成是寡糖合成中最大的挑战之一。复杂碳水化合物的化学合成通常涉及在其异头中心带有离去基团的完全保护的糖基供体与含有亲核试剂（R-OH）的适当保护的糖基受体的偶联。在大多数情况下，这些反应导致两种立体异构体的混合物。最可靠的立体选择性糖基化方法是基于邻基参与（NGP），其需要在C-2位引入特定基团以直接亲核攻击。然而，NGP基团的掺入往往是麻烦的，不切实际的，并不适用于每一种类型的单糖，即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合成2-脱氧半乳糖苷，具有优异的产率和α-选择性。（Angew。（2012），51，36，9152-9155）。拟议的项目旨在开发立体选择性合成糖苷的一般和催化方法。

项目成果

Stereoselective synthesis of protected l- and d-dideoxysugars and analogues via Prins cyclisations.

• DOI: 10.1039/c5sc04144a
• 发表时间: 2016-04-21
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Beattie RJ;Hornsby TW;Craig G;Galan MC;Willis CL
• 通讯作者: Willis CL

Glioma Stem-Like Cells and Metabolism: Potential for Novel Therapeutic Strategies.

• DOI: 10.3389/fonc.2021.743814
• 发表时间: 2021
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 作者: Harland A;Liu X;Ghirardello M;Galan MC;Perks CM;Kurian KM
• 通讯作者: Kurian KM

Carbohydrates as enantioinduction components in stereoselective catalysis.

• DOI: 10.1039/c6ob00368k
• 发表时间: 2016-04-26
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Henderson AS;Bower JF;Galan MC
• 通讯作者: Galan MC