Department of Applied Chemistry, Tokyo Institute of Technology, Japan.
Chemistry. 2013 Feb 25;19(9):3177-87. doi: 10.1002/chem.201203865. Epub 2013 Jan 16.
The synthesis and biological evaluation of the Forssman antigen pentasaccharide and derivatives thereof by using a one-pot glycosylation and polymer-assisted deprotection is described. The Forssman antigen pentasaccharide, composed of GalNAcα(1,3)GalNAcβ(1,3)Galα(1,4)Galβ(1,4)Glc, was recently identified as a ligand of the lectin SLL-2 isolated from an octocoral Sinularia lochmodes. The chemo- and α-selective glycosylation of a thiogalactoside with a hemiacetal donor by using a mixture of Tf(2)O, TTBP and Ph(2)SO, followed by activation of the remaining thioglycoside, provided the trisaccharide at the reducing end in a one-pot procedure. The pentasaccharide was prepared by the α-selective glycosylation of the N-Troc-protected (Troc=2,2,2-trichloroethoxycarbonyl) thioglycoside with a 2-azide-1-hydroxyl glycosyl donor, followed by glycosidation of the resulting disaccharide at the C3 hydroxyl group of the trisaccharide acceptor in a one-pot process. We next applied the one-pot glycosylation method to the synthesis of pentasaccharides in which the galactosamine units were partially and fully replaced by galactose units. Among the three possible pentasaccharides, Galα(1,3)GalNAc and Galα(1,3)Gal derivatives were successfully prepared by the established method. An assay of the binding of the synthetic oligosaccharides to a fluorescent-labeled SLL-2 revealed that the NHAc substituents and the length of the oligosaccharide chain were both important for the binding of the oligosaccharide to SLL-2. The inhibition effect of the oligosaccharide relative to the morphological changes of Symbiodinium by SLL-2, was comparable to their binding affinity to SLL-2. In addition, we fortuitously found that the synthetic Forssman antigen pentasaccharide directly promotes a morphological change in Symbiodinium. These results strongly indicate that the Forssman antigen also functions as a chemical mediator of Symbiodinium.
描述了使用一锅糖苷化和聚合物辅助脱保护法合成 Forssman 抗原五糖及其衍生物，并对其进行了生物学评价。Forssman 抗原五糖由 GalNAcα(1,3)GalNAcβ(1,3)Galα(1,4)Galβ(1,4)Glc 组成，最近被鉴定为从八放珊瑚 Sinularia lochmodes 中分离出的凝集素 SLL-2 的配体。使用 Tf(2)O、TTBP 和 Ph(2)SO 的混合物，对硫代半乳糖苷与半缩醛供体进行选择性的α-糖苷化，然后对剩余的硫代糖苷进行活化，可在一锅法中得到位于还原端的三糖。通过用 2-叠氮-1-羟基糖苷供体对 N-Troc 保护的（Troc=2,2,2-三氯乙氧基羰基）硫代糖苷进行选择性的α-糖苷化，然后在一锅法中对三糖受体的 C3 羟基进行糖苷化，可制备五糖。接下来，我们将一锅糖苷化方法应用于部分和完全用半乳糖基取代氨基半乳糖基的五糖的合成。在三种可能的五糖中，通过已建立的方法成功制备了 Galα(1,3)GalNAc 和 Galα(1,3)Gal 衍生物。对合成寡糖与荧光标记的 SLL-2 结合的测定表明，NHAc 取代基和寡糖链的长度都对寡糖与 SLL-2 的结合至关重要。寡糖相对于 SLL-2 对 Symbiodinium 形态变化的抑制作用与它们与 SLL-2 的结合亲和力相当。此外，我们偶然发现合成的 Forssman 抗原五糖可直接促进 Symbiodinium 的形态变化。这些结果强烈表明 Forssman 抗原也可作为 Symbiodinium 的化学介质。
