School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
Org Biomol Chem. 2020 Oct 14;18(39):7907-7915. doi: 10.1039/d0ob01776k.
Helicobacter spp. are Gram-negative bacteria that cause a spectrum of disease in the gut, biliary tree and liver. Many Helicobacter spp. produce a range of cholesteryl α-glucosides that have the potential to act as pathogen associated molecular patterns. We report a highly stereoselective α-glucosylation of cholesterol using 3,4,6-tri-O-acetyl-2-O-benzyl-d-glucopyranosyl N-phenyl-2,2,2-trifluoroacetimidate, which allowed the synthesis of cholesteryl α-glucoside (αCG) and representative Helicobacter spp. cholesteryl 6-O-acyl-α-glucosides (αCAGs; acyl = C12:0, 14:0, C16:0, C18:0, C18:1). All αCAGs, irrespective of the nature of their acyl chain composition, strongly agonised signalling through the C-type lectin receptor Mincle from human and mouse to similar degrees. By contrast, αCG only weakly signalled through human Mincle, and did not signal through mouse Mincle. These results provide a molecular basis for understanding of the immunobiology of non-pylori Helicobacter infections in humans and other animals.
螺旋菌属是革兰氏阴性细菌，可引起肠道、胆道和肝脏的一系列疾病。许多螺旋菌属产生一系列胆固醇α-葡萄糖苷，具有作为病原体相关分子模式的潜力。我们报告了一种使用 3,4,6-三-O-乙酰-2-O-苄基-d-吡喃葡萄糖基 N-苯基-2,2,2-三氟乙酰胺的高度立体选择性的胆固醇α-葡萄糖苷化，该方法允许合成胆固醇α-葡萄糖苷（αCG）和代表性的螺旋菌属胆固醇 6-O-酰基-α-葡萄糖苷（αCAG；酰基=C12:0、14:0、C16:0、C18:0、C18:1）。所有的αCAG，无论其酰基链组成如何，都强烈地激动了来自人和小鼠的 C 型凝集素受体 Mincle 的信号转导，程度相似。相比之下，αCG 仅微弱地通过人 Mincle 发出信号，并且不通过鼠 Mincle 发出信号。这些结果为理解人类和其他动物中非幽门螺旋菌感染的免疫生物学提供了分子基础。
