A Reagent-Controlled SN2-Glycosylation for the Direct Synthesis of β-Linked 2-Deoxy-Sugars
A Reagent-Controlled SN2-Glycosylation for the Direct Synthesis of β-Linked 2-Deoxy-Sugars
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DOI：
10.1021/ja500410c
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发表时间：
2014-04-16
影响因子：
15
通讯作者：
Bennett, Clay S.
中科院分区：
文献类型：
--
作者：
Issa, John Paul;Bennett, Clay S.
键的高效和立体选择性的构建仍然是有机化学中最艰巨的挑战之一。尤其是在β-连接脱氧糖的情况下，反应的结果不能使用糖基供体固有的立体化学信息来控制。在这里，我们证明了对甲苯磺酸在原位激活2-脱氧糖半缩醛作为亲电物种，它与亲核受体发生立体选择性反应，专一地产生β-异构体。核磁共振研究证实，在这些条件下，半缩醛定量地转化为α-糖基对甲苯磺酸盐，这可能是反应中的活性物种。这种方法表明，使用激活半缩醛的启动子作为明确定义的中间体，可以通过S(N)2途径实现立体选择性糖基化。
The efficient and stereoselective construction of linkages remains one of the most formidable challenges in organic chemistry. This is especially true in cases such as beta-linked deoxy-sugars, where the outcome of the reaction cannot be controlled using the stereochemical information intrinsic to the glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy-sugar hemiacetals in situ as electrophilic species, which react stereoselectively with nucleophilic acceptors to produce beta-anomers exclusively. NMR studies confirm that, under these conditions, the hemiacetal is quantitatively converted into an alpha-glycosyl tosylate, which is presumably the reactive species in the reaction. This approach demonstrates that use of promoters that activate hemiacetals as well-defined intermediates can be used to permit stereoselective glycosylation through an S(N)2-pathway.