New approaches for the stereoselective synthesis of glycans of therapeutic interest

立体选择性合成具有治疗意义的聚糖的新方法

• 批准号: RGPIN-2016-04950
• 负责人: Gauthier, Charles
• 金额: $ 1.82万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632771
• 关键词: New; approaches; stereoselective; synthesis; glycans

It is now recognized that carbohydrates and their conjugates are involved in a plethora of important biological processes such as the immune response and bacterial infections. Well-defined glycans are urgently needed for the in-depth understanding of these mechanisms as well as for the development of sugar-based medicines. In the last years, advances in chemical synthesis have made possible the preparation of complex glycans free from biological contaminants, some of which have been approved as therapeutics. However, carbohydrate chemists are still facing important challenges such as the need for non-traditional and eco-friendly synthetic routes as well as the lack of general procedures for the formation of glycosidic bonds. The long-term goal of our research program is to develop novel and straightforward synthetic approaches to access oligosaccharides and glycoconjugates of therapeutic interest. Our first research theme is to achieve the total synthesis of sponge-derived glycolipids of unique structural features following an innovative “programmed” glycosylation reaction. Found within marine sponges of the New Zealand coral reef, the pharmacological potential of these glycolipids has yet to be explored due to the scarcity of the natural source coupled with the tedious purification procedures. The glycolipids will be synthesized in a minimal number of steps based on the differential reactivity of sugars and evaluated

现在人们认识到，碳水化合物及其缀合物参与了许多重要的生物过程，如免疫反应和细菌感染。为了深入了解这些机制以及开发糖基药物，迫切需要定义明确的聚糖。在过去的几年中，化学合成的进步已经使得制备不含生物污染物的复合聚糖成为可能，其中一些已经被批准作为治疗剂。然而，碳水化合物化学家仍然面临着重要的挑战，例如需要非传统和生态友好的合成路线，以及缺乏形成糖苷键的通用程序。我们研究计划的长期目标是开发新颖和直接的合成方法来获得具有治疗意义的寡糖和糖缀合物。我们的第一个研究主题是通过创新的“程序化”糖基化反应实现具有独特结构特征的海绵糖脂的全合成。在新西兰珊瑚礁的海绵中发现，这些糖脂的药理学潜力尚未被探索，因为天然来源稀缺，加上繁琐的纯化程序。糖脂将根据糖的不同反应性以最少的步骤合成，并进行评价