Synthesis of alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol analogues: polar side-chain modification, sulfonium and selenonium heteroatom variants, conformational analysis, and evaluation as glycosidase inhibitors.
Synthesis of alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol analogues: polar side-chain modification, sulfonium and selenonium heteroatom variants, conformational analysis, and evaluation as glycosidase inhibitors.
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DOI：
10.1021/ja0482076
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发表时间：
2004-09
影响因子：
15
通讯作者：
M. G. Szczepina;B. Johnston;Yue Yuan;B. Svensson;B. Pinto
中科院分区：
文献类型：
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作者：
M. G. Szczepina;B. Johnston;Yue Yuan;B. Svensson;B. Pinto
本文报道了N-烷基化脱氧野尻霉素和具有D-或L-β-3-硫酸酯官能化N-取代基的1，5-双脱氧-1，5-亚氨基肌醇衍生物的合成。所用的烷基化剂是环状硫酸酯衍生物，由此在最小位阻的伯中心处选择性攻击氮原子，得到所需的铵盐。在水溶液中，这些盐在铵中心的构型不稳定。铵盐的锍和/或硒类似物通过类似反应制备。硫族元素盐以非对映异构体的混合物形式获得，在某些情况下是可分离的，不同之处仅在于构型稳定的硫或硒原子的立体化学。通过详细的NMR实验获得了每个化合物的构型和构象的证明。这些化合物是已知的锍盐葡萄糖苷酶抑制剂水杨酸的六元环类似物。对目标化合物对葡糖苷酶葡糖淀粉酶G2的酶抑制的评价表明，这些化合物或者是无活性的，或者充其量只是麦芽糖水解的弱抑制剂。
The syntheses of N-alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol derivatives having either a D- or an L-erythritol-3-sulfate functionalized N-substituent are reported. The alkylating agent used was a cyclic sulfate derivative, whereby selective attack of the nitrogen atom at the least hindered primary center afforded the desired ammonium salt. In aqueous solution, these salts were configurationally labile at the ammonium center. Sulfonium and/or selenonium analogues of the ammonium salts were prepared by analogous reactions. The chalcogen salts were obtained as mixtures of diastereomers, separable in some cases, differing only in the stereochemistry at the configurationally stable sulfur or selenium atoms. Proof of configuration and conformation of each compound was obtained by detailed NMR experiments. The compounds are six-membered ring analogues of salacinol, a known sulfonium-salt glucosidase inhibitor. Evaluation of the target compounds for enzyme inhibition of the glucosidase enzyme glucoamylase G2 indicated that these compounds were either inactive or, at best, only weak inhibitors of maltose hydrolysis.