A highly convergent total synthetic route to glycopeptides carrying a high-mannose core pentasaccharide domain N-linked to a natural peptide motif
A highly convergent total synthetic route to glycopeptides carrying a high-mannose core pentasaccharide domain N-linked to a natural peptide motif
复制标题
DOI：
10.1002/chem.19970031011
复制
发表时间：
1997-10-01
影响因子：
4.3
通讯作者：
Seeberger, PH
中科院分区：
文献类型：
--
作者：
Danishefsky, SJ;Hu, S;Seeberger, PH
N-连接糖肽是由带有五糖的高甘露糖异头胺与含天冬氨酸的三肽和五肽通过IIDQ缩合而合成的。对应于所有天冬酰胺连接的糖蛋白的“核心"区域的五糖部分通过糖衍生的硫代乙基供体和糖受体组装。中心甘露糖残基通过戊糖中葡糖基前体的C2羟基的反转来建立。所采用的保护基方案允许戊糖通过末端甘露糖单元延伸。虽然高甘露糖碳水化合物与肽结构域的完全会聚偶联因此首次用完全合成的糖完成，但碳水化合物结构域的异头中心的立体化学完整性没有保持，并且获得了糖肽的混合物。
N-Linked glycopeptides were synthesized by condensation of a high-mannose anomeric amine bearing a pentasaccharide with aspartic-acid-containing tri-and pentapeptides through the agency of IIDQ. The pentasaccharide portion, corresponding to the ''core'' region of all asparagine-linked glycoproteins, was assembled by means of glycal-derived thioethyl donors and glycal accepters. The central mannose residue was established by inversion of the C 2 hydroxyl of a glucosyl precursor in the pentasaccharide, The protecting-group scheme employed allows the extension of the pentasaccharide through the terminal mannose units. While a fully convergent coupling of the high-mannose carbohydrate to the peptide domain has thus been accomplished for the first time with a fully synthetic sugar, the stereochemical integrity of the anomeric center of the carbohydrate domain was not maintained and a mixture of glycopeptides was obtained.