Liao Liang, Auzanneau France-Isabelle
Department of Chemistry, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
J Org Chem. 2005 Aug 5;70(16):6265-73. doi: 10.1021/jo050707+.
Glycosylation of a disaccharide containing N-acetylglucosamine with rhamnosyl and mannosyl trichloracetimidates under triethysilyl triflate catalysis led to the competitive formation of glycosyl imidates. While the rhamnosyl imidate could be rearranged to the thermodynamically favored trisaccharide, the mannosyl analogue was resistant to rearrangement. Glycosylation with perbenzylated thiorhamnosides activated with methyl triflate (MeOTf) gave the trisaccharide as well as the methyl imidate trisaccharide. The less reactive alpha-thioethyl donor led to a higher relative amount of methyl imidate trisaccharide to trisaccharide than the more reactive beta-thioglycoside. When using a more reactive thioethyl fucoside only the trisaccharide was obtained. Interestingly, the acceptor treated with MeOTf gave the N-methyl imidate that could be easily rhamnosylated and subsequently converted to the N-acetamido trisaccharide. This strategy to glycosylate O-4 of N-acetylglucosamine is under further investigation. Alternatively, bis-N-acetylation of the glucosamine prevented the formation of imidates and allowed the efficient synthesis of two Lewis A trisaccharide analogues.
在三乙基甲硅烷基三氟甲磺酸酯催化下，含N - 乙酰葡糖胺的二糖与鼠李糖基和甘露糖基三氯乙酰亚胺进行糖基化反应，导致糖基亚胺的竞争性形成。虽然鼠李糖基亚胺可以重排为热力学上更稳定的三糖，但甘露糖基类似物对重排具有抗性。用三氟甲磺酸甲酯（MeOTf）活化的全苄基化硫代鼠李糖苷进行糖基化反应，得到了三糖以及甲基亚胺基三糖。反应活性较低的α - 硫代乙基供体与反应活性较高的β - 硫代糖苷相比，生成的甲基亚胺基三糖与三糖的相对量更高。当使用反应活性更高的硫代乙基岩藻糖苷时，仅得到了三糖。有趣的是，用MeOTf处理的受体得到了N - 甲基亚胺，它可以很容易地进行鼠李糖基化，随后转化为N - 乙酰氨基三糖。这种对N - 乙酰葡糖胺的O - 4进行糖基化的策略正在进一步研究中。另外，葡糖胺的双N - 乙酰化可防止亚胺的形成，并允许高效合成两种Lewis A三糖类似物。
