Stereoselectivity of Conformationally Restricted Glucosazide Donors.
Stereoselectivity of Conformationally Restricted Glucosazide Donors.
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DOI：
10.1021/acs.joc.7b00470
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发表时间：
2017-05-05
期刊：
影响因子：
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通讯作者：
Codée JDC
中科院分区：
文献类型：
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作者：
van der Vorm S;Overkleeft HS;van der Marel GA;Codée JDC
用一组模型受体对4，6-栓联葡糖酰肼供体进行糖基化，揭示了受体亲核性对这些供体的立体选择性的影响。在竞争性糖基化反应中评价了供体之间反应性的差异，发现它们的相对反应性反映在与一组氟化醇以及碳水化合物受体的糖基化的立体选择性中。我们发现2-叠氮基-2-脱氧部分比其C-2-O-苄基对应物更具有β-定向性，这是由于吸电子叠氮化物增加了异头电荷发展的不稳定性。额外的解除武装基团进一步降低了所研究的供体的α-选择性，而用4，6-二叔丁基甲硅烷基取代4，6-亚苄基缩醛导致α-选择性略有增加。还探索了C-2-二硝基吡啶酮基团作为非参与叠氮基团的替代物，但该保护基团显著增加了β-选择性。所有研究的给体都表现出相同的受体依赖性选择性趋势，并且最弱的受体和最活跃的给体可以获得良好的α-选择性。
Glycosylations of 4,6-tethered glucosazide donors with a panel of model acceptors revealed the effect of acceptor nucleophilicity on the stereoselectivity of these donors. The differences in reactivity among the donors were evaluated in competitive glycosylation reactions, and their relative reactivities were found to be reflected in the stereoselectivity in glycosylations with a set of fluorinated alcohols as well as carbohydrate acceptors. We found that the 2-azido-2-deoxy moiety is more β-directing than its C-2-O-benzyl counterpart, as a consequence of increased destabilization of anomeric charge development by the electron-withdrawing azide. Additional disarming groups further decreased the α-selectivity of the studied donors, whereas substitution of the 4,6-benzylidene acetal with a 4,6-di-tert-butyl silylidene led to a slight increase in α-selectivity. The C-2-dinitropyridone group was also explored as an alternative for the nonparticipating azide group, but this protecting group significantly increased β-selectivity. All studied donors exhibited the same acceptor-dependent selectivity trend, and good α-selectivity could be obtained with the weakest acceptors and most reactive donors.