Hsieh Hsiao-Wu, Davis Ryan A, Hoch Jessica A, Gervay-Hague Jacquelyn
Department of Chemistry, University of California, Davis, One Shields Ave., Davis, CA 95616 (USA), Fax: (+1) 530-754-6915.
Chemistry. 2014 May 19;20(21):6444-54. doi: 10.1002/chem.201400024. Epub 2014 Apr 8.
Oligosaccharide conjugates, such as glycoproteins and glycolipids, are potential chemotherapeutics and also serve as useful tools for understanding the biological roles of carbohydrates. With many modern isolation and synthetic technologies providing access to a wide variety of free sugars, there is increasing need for general methodologies for carbohydrate functionalization. Herein, we report a two-step methodology for the conjugation of per-O-acetylated oligosaccharides to functionalized linkers that can be used for various displays. Oligosaccharides obtained from both synthetic and commercial sources were converted to glycosyl iodides and activated with I2 to form reactive donors that were subsequently trapped with trimethylene oxide to form iodopropyl conjugates in a single step. The terminal iodide served as a chemical handle for further modification. Conversion into the corresponding azide followed by copper-catalyzed azide-alkyne cycloaddition afforded multivalent glycoconjugates of Gb3 for further investigation as anti-cancer therapeutics.
寡糖缀合物，如糖蛋白和糖脂，是潜在的化学治疗药物，也是理解碳水化合物生物学作用的有用工具。随着许多现代分离和合成技术能够获取各种各样的游离糖，对碳水化合物功能化通用方法的需求日益增加。在此，我们报道了一种两步法，用于将全O-乙酰化寡糖与可用于各种展示的功能化连接子进行缀合。从合成和商业来源获得的寡糖被转化为糖基碘化物，并用I2活化以形成反应性供体，随后用环氧丙烷捕获，一步形成碘丙基缀合物。末端碘化物作为进一步修饰的化学手柄。转化为相应的叠氮化物，然后通过铜催化的叠氮化物-炔烃环加成反应得到Gb3的多价糖缀合物，用于作为抗癌治疗药物的进一步研究。
