Instituto de Investigaciones Químicas, Centro de Investigaciones Científicas Isla de La Cartuja, CSIC -US, Americo Vespucio, 49, 41092 Sevilla, Spain.
Carbohydr Res. 2010 Mar 30;345(5):565-71. doi: 10.1016/j.carres.2009.12.021. Epub 2010 Jan 4.
The synthesis of hyaluronic acid oligosaccharides on polyethylene glycol (PEG) using an acylsulfonamide linker has been explored. Hyaluronic acid is a challenging synthetic target that usually involves the condensation of highly disarmed glucuronic acid building blocks. Amine-ended PEG monomethyl ether was efficiently functionalized with a hydroxyl-terminated acylsulfonamide linker. Suitably protected D-glucosamine (GlcN) and D-glucuronic acid (GlcA) monosaccharide building blocks were coupled to the polymer acceptor using the trichloroacetimidate glycosylation method. The sulfonamide safety-catch linker enables simultaneous cleavage of the monosaccharide from the polymer and orthogonal functionalization for further (bio)-conjugation of the sugar sample. Subsequent glycosylation of PEG-bound glycosyl acceptor to generate hyaluronic acid oligosaccharide chain failed. Model glycosylation experiments in solution and on soluble support using the same unreactive acceptors and donors allows for the synthesis of an orthogonally protected hyaluronic acid disaccharide and suggest that the encountered difficulties could be attributed to the presence of the N-acylsulfonamide.
已探索在聚乙二醇（PEG）上使用酰基磺酰胺键合连接物合成透明质酸低聚糖。透明质酸是一个具有挑战性的合成目标，通常涉及高度去保护的葡萄糖醛酸构建块的缩合。胺封端的 PEG 单甲醚通过羟基封端的酰基磺酰胺键合连接物有效地进行功能化。适当保护的 D-葡萄糖胺（GlcN）和 D-葡萄糖醛酸（GlcA）单糖构建块通过三氯乙酰亚胺酯糖基化方法偶联到聚合物受体上。磺酰胺安全捕获键合连接物允许糖从聚合物上同时裂解，并进行正交官能化，从而进一步对糖样品进行（生物）偶联。随后，PEG 键合的糖基受体上的糖基化反应生成透明质酸低聚糖链失败。在溶液中和可溶性载体上使用相同的非反应性受体和供体进行模型糖基化实验，可合成正交保护的透明质酸二糖，并表明遇到的困难可能归因于 N-酰基磺酰胺的存在。
