New approaches for the stereoselective synthesis of glycans of therapeutic interest

现在人们认识到，碳水化合物及其结合物参与了大量重要的生物过程，如免疫反应和细菌感染。为了深入了解这些机制以及开发以糖为基础的药物，迫切需要定义明确的葡聚糖。在过去的几年里，化学合成的进步使得制备不受生物污染的复合多糖成为可能，其中一些已经被批准用于治疗。然而，碳水化合物化学家仍然面临着重要的挑战，例如需要非传统和环保的合成路线，以及缺乏形成糖苷键的一般程序。我们研究计划的长期目标是开发新的和直接的合成方法来获得有治疗意义的寡糖和糖结合物。我们的第一个研究主题是通过创新的“程序化”糖基化反应，实现海绵衍生的具有独特结构特征的糖脂的全合成。在新西兰珊瑚礁的海绵中发现了这些糖脂，但由于天然来源的稀缺加上繁琐的纯化程序，这些糖脂的药理潜力尚未被探索。糖脂将根据糖的不同反应性以最少的步骤合成并进行评估

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