SYNTHESIS OF STABLE GALACTO DISACCHARIDE MIMETICS

人们对模拟碳水化合物的分子很感兴趣。 参与与健康障碍相关的机制。碳水化合物 外环或内环缩醛氧被取代的类似物 分别由亚甲基、C-糖苷或碳糖吸引 利息。预计这些分子具有相似的构象。 和空间性质，因此具有相似的连接特性 作为天然的O-糖。重要的是，它们不是糖苷，而且 因此对糖基加工酶和化学物质都是稳定的 水解液。它们可能作为治疗剂或工具有用。 用于生化研究。 这个项目涉及合成三个化合物的新方法。 模拟糖的基团：半乳糖的糖苷和碳糖 糖苷和糖苷(GPI)亚基的C-糖苷。这个 具体目标是：(I)潜在的I选择素C-糖苷 并可为设计新颖的， 水解性，稳定的抗炎剂。(Ii)C-糖苷和 半乳糖-β-二糖的碳糖，它是 糖基加工酶稳定络合物的制备及可能 具有抑制作用。(Iii)GPI的C-糖苷类似物 与GPI相关的调查相关的组件 过程，如寄生原生动物的生存机制和信号 与胰岛素作用相关的转导。 合成策略以硫代化合物的新化学为中心。 异丙基缩醛(TIA)。该方法非常适合于制作 双糖模拟物，尽管它可能同样容易应用于 单糖结构。制造二糖类似物的概念 包括环糖衍生物与TIA的初始连接 合唱团。随后，第二环由氧碳正离子形成 离子-烯烃环化得到二氢吡喃或环己烯衍生物， 取决于所使用的TIA片段的选择。立体选择 烯烃的官能化导致目标糖仿制。 该策略为耦合效率问题提供了解决方案 和立体选择性，这限制了两个完整的 环状糖衍生物。

There is considerable interest in molecules which mimic carbohydrates involved in mechanisms associated with health disorders. Carbohydratees analogs in which the exocyclic or endocyclic acetal oxygen is replaced by a methylene, C-glycoside or carbasugar respectively have attracted interest. These molecules are expected to have similar conformational and steric properties, and therefore similar ligating characteristics as the natural O-saccharide. Importantly, they are not glycosides and therefore will be stable to glycosyl processing enzymes and to chemical hydrolysis. They are potentially useful as therapeutic agents or tools for biochemical research. This project deals with new methodology for the synthesis of three groups of glycomimetics: C-glycosides and carbasugars of Galbeta glycosides, and C-glycosides of glycophospatidyl (GPI) subunits. The specific aims are: (I) C-glycosides which are potential Iselectin ligands and could provide the basis for the design of novel, hydrolytically, stable anti-inflammatory agents. (II) C-Glycosides and carbasugars of Gal-beta-disaccharides, which are substrates for preparation of stable complexes with glycosyl processing enzymes and may have inhibitory properties. (III) C-glycoside analogs of GPI components, which are relevant to the investigation of GPI related processes, such as survival mechanisms in parasitic protozoa and signal transduction related to insulin action. The synthetic strategy centers on novel chemistry of thio- isopropylidinated acetals (TIA's). The method is well suited for making disaccharide mimetics, although it may be just as easily applied to monosaccharide structures. The concept for making disaccharide analogs involves the initial linking of a cyclic sugar derivative to a TIA synthon. Subsequently, the second ring is formed by an oxocarbenium ion-alkene cyclization to give a dihydropyran or cyclohexene derivative, depending on the choice of the TIA fragment used. Stereoselective functionalization of the alkene leads to the targeted glycomimetics. This strategy provides solutions to the problems of coupling efficiency and stereoselectivity which limit the direct connection of two intact cyclic sugar derivatives.