具神經再生活性之醣苷神經鞘胺酯質的研究:醣苷神經鞘胺酯質DSG-1之類似物DSG-1a的合成

Abstract

The diseases caused by the nerve degeneration and never damage bring humanity big trouble. For this reason, It is emergent to search and develop efficient methods or efficacious drugs to enhance never regeneration for scientists. Ganglioside DSG-1, isolated from the the ovary of the sea urchin Diadema setosum, and possesses NeuAc (N-acetylneuraminic acid) α2→6Glcβ1→1Cer, displays neuritogenic activity toward the rat pheochromocytoma cell line PC-12 cell in the presence of NGF. Due to the difficulty of observing enough purity and amount of DSG-1 from natural resources for clinical use, none of related synthesis in literatures, we propose to chemically prepare the DSG-1 compound and its analogues DSG-1a and then explore the bioactivity of never regeneration. However, the difference between DSG-1a and DSG-1 is the length of carbon chain of phytosphingosine moiety. The length of carbon chain of phytosphingosine is seventeen carbons for DSG-1a and eighteen carbons for DSG-1. To develop the one-pot two-step glycosylations to conform the essence of “Green Chemistry” for the synthetic methods, we adopt the orthogonal leaving-group stratagey. That is we assemble a leaving group PhS- at anomeric carbon of Neu-3 and introduce TazS- as leaving group at anomeric carbon of Glc-15. Glycosylation of glycosyl donor Neu-3 with glycosyl acceptor Glc-15 afforded a disaccharide NG-1 as a ca. 3.2:1.0 in mixture of α- and β-stereoisomers in 63% yield. The disaccharides containing phytosphingosine NGL-1αβ and NGL-1ββ (62% yield) were prepared by the glycosylation of disaccharide NG-1 and phytosphingosine derivative LYX-9 and the stereochemistry of glucose moiety was single β -configuration. The synthesis of the target compound DSG-1a was achieved by the amidization, debenzylation, and deacetylation of NGL-1αβ.