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首页> 外文期刊>Chemistry: A European journal >Efficient Atropodiastereoselective Access to 5,5' -Bis-1,2,3-triazoles: Studies on 1-Glucosylated 5-Halogeno 1,2,3-Triazoles and Their 5-Substituted Derivatives as Glycogen Phosphorylase Inhibitors
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Efficient Atropodiastereoselective Access to 5,5' -Bis-1,2,3-triazoles: Studies on 1-Glucosylated 5-Halogeno 1,2,3-Triazoles and Their 5-Substituted Derivatives as Glycogen Phosphorylase Inhibitors

机译：有效地对5,5'-Bis-1,2,3-三唑类化合物进行对映体对映选择性的研究：1-糖基化的5-Halogeno 1,2,3-三唑类化合物及其5-取代的衍生物作为糖原磷酸化酶抑制剂的研究

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Whereas copper-catalyzed azide-alkyne cycloaddition (CuAAC) between acetylated β-D-glucosyl azide and alkyl or phenyl acetylenes led to the corresponding 4-substi-tuted 1 -glucosyl-1,2,3-triazoles in good yields, use of similar conditions but with 2 equiv Cul or CuBr led to the 5-halo-geno analogues (>71 %). In contrast, with 2 equiv CuCI and either propargyl acetate or phenyl acetylene, the major products (> 56%) displayed two 5,5'-linked triazole rings resulting from homocoupling of the 1 -glucosyl-4-substituted 1,2,3-triazoles. The 4-phenyl substituted compounds (acetylated, O-unprotected) and the acetylated 4-acetoxymethyl derivative existed in solution as a single form (d.r.>95:5), as shown by NMR spectroscopic analysis. The two 4-phenyl substituted structures were unambiguously identified for the first time by X-ray diffraction analysis, as atropisomers with aR stereochemistry. This represents one of the first efficient and highly atropodiastereoselective approaches to glucose-based bis-triazoles as single atropisomers. The products were purified by standard silica gel chromatography. Through Sonogashira or Suzuki cross-couplings, the 1-gluco-syl-5-halogeno-1,2,3-triazoles were efficiently converted into a library of 1,2,3-triazoles of the 1 -glucosyl-5-substituted (alkynyl, aryl) type. Attempts to achieve Heck coupling to methyl acrylate failed, but a stable palladium-associated triazole was isolated and analyzed by ~1H NMR and MS. O-Unprotected derivatives were tested as inhibitors of glycogen phosphorylase. The modest inhibition activities measured showed that 4,5-disubstituted 1-glucosyl-1,2,3-triazoles bind weakly to the enzyme. This suggests that such ligands do not fit the catalytic site or any other binding site of the enzyme.
机译：乙酰化的β-D-葡糖基叠氮化物与烷基或苯基乙炔之间的铜催化的叠氮化物-炔烃环加成反应（CuAAC）导致相应的4-取代的1-葡糖基-1,2,3-三唑的高收率，在相似的条件下，但使用2当量的Cul或CuBr生成5-卤代基因类似物（> 71％）。相比之下，在使用2当量的CuCl和乙酸炔丙酯或苯基乙炔的情况下，主要产物（> 56％）显示出由1-葡萄糖基4取代的1,2,3均偶联而形成的5,5'-连接的三唑环。 -三唑。如NMR光谱分析所示，4-苯基取代的化合物（乙酰化的，O-未保护的）和乙酰化的4-乙酰氧基甲基衍生物以单一形式（d.r.＞ 95∶5）存在于溶液中。通过X射线衍射分析首次明确地确定了两个4-苯基取代的结构为具有aR立体化学的阻转异构体。这代表了基于葡萄糖的双三唑作为单一阻转异构体的首批有效且高度对映体非对映选择性的方法之一。产物通过标准硅胶色谱纯化。通过Sonogashira或Suzuki交叉偶联，可将1-葡萄糖-syl-5-卤代-1,2,3-三唑有效地转化为1-葡萄糖--5-取代的1,2,3-三唑的文库（炔基，芳基）类型。未能实现与丙烯酸甲酯的Heck偶联，但分离出了稳定的钯相关三唑并通过〜1H NMR和MS进行了分析。测试了O-未保护的衍生物作为糖原磷酸化酶的抑制剂。测得的适度抑制活性表明4，5-二取代的1-葡萄糖基-1,2,3-三唑与酶的结合较弱。这表明此类配体不适合酶的催化位点或任何其他结合位点。

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