Department of Chemistry, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.
Beilstein J Org Chem. 2010 Feb 22;6:17. doi: 10.3762/bjoc.6.17.
The synthesis of three Le(x) derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N-acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40° C under excess of BF₃.OEt₂ activation and proceeded best if the acceptor carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Le(x) trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6-acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70-95%). In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led respectively to the n-hexyl and 6-aminohexyl trisaccharide targets. Unexpectedly, the 6-acetylthiohexyl analogue underwent desulfurization and gave the n-hexyl glycoside product, whereas the 6-benzylthiohexyl analogue gave the desired disulfide trisaccharide dimer. This study constitutes a particularly efficient and convergent preparation of these three Le(x) analogues.
报道了一种从一个共同保护的三糖合成三种 Le(x)衍生物的方法。这些类似物将分别用于竞争性结合实验、与载体蛋白的缀合以及固定在金上。首先，在 BF₃.OEt₂过量激活下，将 N-乙酰葡萄糖胺单糖受体在 O-4 位与半乳糖亚氨基糖苷化。如果受体带有 6-氯己基而不是 6-叠氮己基糖苷，该偶联反应在 40°C 下进行得最好。然后，将 6-氯己基二糖转化为受体并进行岩藻糖基化，得到相应的保护 6-氯己基 Le(x)三糖。该保护三糖用作 6-叠氮己基、6-乙酰巯基己基和 6-苯甲基巯基己基三糖类似物的前体，这些类似物的产率非常高（70-95%）。反过来，我们描述了使用溶解金属条件在一步中对这些中间体进行脱保护。在这些条件下，6-氯己基和 6-叠氮己基中间体分别得到正己基和 6-氨基己基三糖靶标。出乎意料的是，6-乙酰巯基己基类似物发生脱硫反应，得到正己基糖苷产物，而 6-苯甲基巯基己基类似物则得到所需的二硫代三糖二聚体。这项研究构成了这些三种 Le(x)类似物的特别有效和收敛的制备方法。
