通过紫外光促进的脱巯基反应高立体选择性合成2-脱氧糖苷

Deoxy glycosides are frequently the main constituents of glycosidic chains in many biologically active natural products, including antibiotics and cardiac glycosides, in which they are thought to play significant roles in bioactivity. Consequently, the synthesis of deoxy sugars and further synthesis of related natural products, particularly 2-deoxy glycosides and their derivatives, has been identified as an important and challenging area of carbohydrate chemistry. Several deoxy sugar production methods have been reported, including the reduction of glycals, glyco-epoxides, and glycosides with halides and thiocarbonyl groups, all of which have their respective advantages and shortcomings. We recently found a UV light-triggered desulfurization method whereby sulfur-containing glycosides could be completely desulfurized within 0.5 h at room temperature and in the presence of trialkylphosphines. This method can be used to synthesize various deoxy glycosides. Desulfurization is rarely applied to the synthesis of deoxy glycosides, possibly because of a lack of efficient means to obtain sulfur-containing glycosides. In this project, we plan to explore the efficient method of deoxy glycoside synthesis via desulfurization of sulfur-containing glycosides. More importantly, because C-2 thio-acetate group participation can effectively control the stereochemistry of disaccharide formation, it should be simple to construct 2-deoxy disaccharides with excellent stereoselectivity via a glycosylation donor with a C-2 thioacetate group, followed by efficient desulfurization.

脱氧糖特别是2-脱氧糖具有重要生物功能，也是很多天然产物中重要的结构单元，经常出现在强心苷、抗生素及抗癌药物中，所以它们及其相关天然产物的合成，一直被认为是糖化学中重要和具有挑战性的领域。常用合成脱氧糖方法包括糖环上烯键、环氧键、卤基及含硫基团的还原，各有优缺点。而在合成2-脱氧糖苷的糖基化过程中，2位羟基的缺失使得有效控制脱氧糖糖苷键的构型成为一个难点。我们最近发现了一种紫外光促进的脱巯基反应，可以用于合成脱氧糖，具有安全易控、反应时间短、收率高的优点。基于此我们设想了一种利用含2-硫乙酰基的糖基供体来合成立体选择性单一的2-脱氧糖苷的策略。我们拟先利用双转型策略高效合成含2-硫乙酰基的糖基供体，再利用糖基供体与受体的糖基化反应合成糖苷，因2-硫乙酰基的强邻基参与效应，糖苷键的立体选择性可被有效控制。产物经紫外光促进的脱巯基反应后，立体选择性单一的2-脱氧糖苷就可被高效合成。

脱氧糖特别是2-脱氧糖具有重要生物功能，其结构单元出现在多种天然产物中，也是强心苷、某些抗生素和抗癌药物的核心结构。脱氧糖及其相关天然产物的合成，一直是糖化学研究中的重要领域，而2-脱氧寡糖的合成是其中的一个重要挑战。在2-脱氧寡糖合成的糖基化过程中，2-脱氧糖基供体的2位羟基的缺失使得有效控制糖苷键的绝对构型成为一个难点。在本项目中，我们基于紫外光促进的脱巯基反应来发展脱氧糖合成策略。我们将硫乙酰基的选择性酰基脱除和紫外光促进的脱巯基反应结合起来，发展了一种紫外光促进的脱硫乙酰基的一锅法策略，该策略安全易控、反应时间短、收率高。我们应用该策略合成了具有绝对构型的2-脱氧寡糖。为了在2-脱氧寡糖合成中控制生成的糖苷键的构型，我们设计并利用双转型策略高效合成了一系列含2-硫乙酰基的糖基供体。在含2-硫乙酰基的糖基供体与受体的糖基化反应中，因2-硫乙酰基的强邻基参与效应，从而有效控制了生成的糖苷键的立体选择性。得到的立体选择性单一的糖基化产物经一锅法脱硫乙酰基策略被脱除了硫乙酰基，具有绝对构型的2-脱氧寡糖就被高效合成出来。另外，我们在糖羟基的选择性保护方面也做了很多工作。本项目在执行期间共发表基金标注论文13篇，其中在影响因子不低于4.0的期刊上发表论文10篇，申请发明专利两项。