Cheng Anderson, Hendel Jenifer L, Colangelo Kimberley, Bonin Michael, Auzanneau France-Isabelle
Department of Chemistry, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.
J Org Chem. 2008 Oct 3;73(19):7574-9. doi: 10.1021/jo801117y. Epub 2008 Sep 4.
This paper expands on the scope and utility of the temporary conversion of N-acetyl groups to alkyl imidates when attempting to glycosylate at O-4 of N-acetylglucosamine acceptors. The optimized synthesis of alkyl imidate protected glucosamine acceptors at position 4 and carrying various protecting groups at O-3 is described. These imidates were prepared immediately prior to glycosylation by treating the 4-OH acceptors with 0.5 M MeOTf to obtain the corresponding methyl imidates still carrying a free 4-OH group. When preparing these imidates in diethyl ether as the reaction solvent, we observed the unexpected formation of ethyl imidates in addition to the desired methyl imidates. While the 3-O-allyl acceptors were too unstable to be useful in glycosylation reactions, the 3-O-acylated methyl and ethyl imidates of glucosamine were shown to behave well during the glycosylation of the 4-OH with a variety of reaction conditions and various glycosyl donors. Glycosylation of these acceptors was successfully carried out with perbenzylated beta-thioethyl rhamnopyranoside under MeOTf promotion, while activation of this donor under NIS/TMSOTf or NIS/TfOH proved less successful. In contrast, activation of the less reactive perbenzylated alpha-thioethyl and peracetylated beta-thioethyl rhamnopyranosides with NIS/TfOH led to successful glycosylations of the 4-OH. Activation of a peracetylated rhamnosyl trichloroacetimidate by TMSOTf at low temperature also gave a high yield of glycosylation. We also report one-pot glycosylation reactions via alkyl imidate protected acceptor intermediates. In all cases the alkyl imidate products were readily converted to their corresponding N-acetyl derivatives under mild conditions.
本文拓展了在尝试对N-乙酰葡糖胺受体的O-4位进行糖基化时，将N-乙酰基临时转化为烷基亚氨酸酯的范围和实用性。描述了在O-3位带有各种保护基的4位烷基亚氨酸酯保护的葡糖胺受体的优化合成方法。这些亚氨酸酯是在糖基化反应即将进行之前，通过用0.5 M三氟甲磺酸甲酯处理4-OH受体来制备的，以得到仍带有游离4-OH基团的相应甲基亚氨酸酯。当在二乙醚作为反应溶剂中制备这些亚氨酸酯时，我们观察到除了所需的甲基亚氨酸酯外，意外地形成了乙基亚氨酸酯。虽然3-O-烯丙基受体在糖基化反应中过于不稳定而无法使用，但葡糖胺的3-O-酰化甲基和乙基亚氨酸酯在4-OH与各种反应条件和各种糖基供体的糖基化过程中表现良好。这些受体的糖基化在三氟甲磺酸甲酯促进下，用全苄基化的β-硫代乙基鼠李吡喃糖苷成功进行，而在N-碘代琥珀酰亚胺/三甲基甲硅烷基三氟甲磺酸酯或N-碘代琥珀酰亚胺/三氟甲磺酸作用下对该供体的活化效果较差。相比之下，用N-碘代琥珀酰亚胺/三氟甲磺酸对活性较低的全苄化基化α-硫代乙基和全乙酰化β-硫代乙基鼠李吡喃糖苷进行活化，导致4-OH的糖基化成功。在低温下用三甲基甲硅烷基三氟甲磺酸酯对全乙酰化鼠李糖基三氯乙亚氨酸酯进行活化，也得到了高产率的糖基化产物。我们还报道了通过烷基亚氨酸酯保护的受体中间体进行的一锅法糖基化反应。在所有情况下，烷基亚氨酸酯产物在温和条件下很容易转化为它们相应的N-乙酰基衍生物。
