唾液酸化 Lewis-O-核心-1 苏氨酸的汇聚合成。
Convergent Synthesis of Sialyl Lewis- O-Core-1 Threonine.
机构信息
Department of Surgery, Center for Drug Discovery and Translational Research , Beth Israel Deaconess Medical Center, Harvard Medical School , 110 Francis Street, Suite 9F , Boston , Massachusetts 02215 , United States.
Wyss Institute of Biologically Inspired Engineering , Harvard University , 110 Francis Street, Suite 9F , Boston , Massachusetts 02115 , United States.
出版信息
J Org Chem. 2018 May 4;83(9):4963-4972. doi: 10.1021/acs.joc.7b03117. Epub 2018 Apr 23.
Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl Lewis (sLe) linked to a Core-1- O-hexasaccharide 1, as a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using α-selective sialylation and a regioselective [4+2] glycosylation are the key features of this synthesis.
选择素是一类细胞黏附分子，在炎症的初始阶段发挥着关键作用。P 选择素糖蛋白配体-1（PSGL-1）的 N 端结构域与所有选择素结合，但与 P 选择素的亲和力最高。最近的证据表明，阻断 P 选择素/PSGL-1 相互作用为治疗许多炎症性疾病提供了可行的治疗选择。在此，我们报告了含有苏氨酸的唾液酸化 sialyl Lewis（sLe）连接到核心-1-O-六糖 1 的全合成，这是 PSGL-1 N 端结构域的关键聚糖。使用α-选择性唾液酸化和区域选择性[4+2]糖基化的聚合合成是该合成的关键特征。
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