(2S,3S,4R)-N-tert-butoxycarbonyl-2-azidomethyl-3,4-O-isopropylidenepyrrolidine-3,4-diol | 1415972-59-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S,3S,4R)-N-tert-butoxycarbonyl-2-azidomethyl-3,4-O-isopropylidenepyrrolidine-3,4-diol
• CAS: 1415972-59-6
• 化学式: C₁₃H₂₂N₄O₄
• 分子量: 298.342
• InChiKey: VERAOYMPEYXZPL-AEJSXWLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  96.76
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (2S,3S,4R)-N-tert-butoxycarbonyl-2-azidomethyl-3,4-O-isopropylidenepyrrolidine-3,4-diol 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 7.5h， 生成
  参考文献：
  名称：

  Tuning of β-glucosidase and α-galactosidase inhibition by generation and in situ screening of a library of pyrrolidine-triazole hybrid molecules

  摘要：

  The preliminary screening of two libraries of epimeric (pyrrolidin-2-yl)triazoles (14a-s and 22a-s), generated via click chemistry, allowed the rapid identification of four alpha-galactosidase (coffee beans) inhibitors (22b,k,p,r) and two beta-glucosidase (almond) inhibitors (14b,f) in the low mu M range. The additional biological analysis of 14b,f towards beta-glucocerebrosidase (human lysosomal beta-glucosidase), as target enzyme for Gaucher disease, showed a good correlation with the inhibition results obtained for the plant (almond) enzyme. Surprisingly, although these compounds showed inhibition towards beta-glucocerebrosidase as acid hydrolase, they did not inhibit bovine liver beta-glucosidase as neutral hydrolase. In contrast to what was observed for beta-glucosidase inhibition, the coffee bean alpha-galactosidase inhibitors of the epimeric library (22b,k,p,r) only showed weak inhibition towards human lysosomal alpha-galactosidase. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.055
• 作为产物：
  描述：

  N-benzyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-talitol 在 吡啶 、 sodium tetrahydroborate 、 sodium periodate 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.83h， 生成 (2S,3S,4R)-N-tert-butoxycarbonyl-2-azidomethyl-3,4-O-isopropylidenepyrrolidine-3,4-diol
  参考文献：
  名称：

  Tuning of β-glucosidase and α-galactosidase inhibition by generation and in situ screening of a library of pyrrolidine-triazole hybrid molecules

  摘要：

  The preliminary screening of two libraries of epimeric (pyrrolidin-2-yl)triazoles (14a-s and 22a-s), generated via click chemistry, allowed the rapid identification of four alpha-galactosidase (coffee beans) inhibitors (22b,k,p,r) and two beta-glucosidase (almond) inhibitors (14b,f) in the low mu M range. The additional biological analysis of 14b,f towards beta-glucocerebrosidase (human lysosomal beta-glucosidase), as target enzyme for Gaucher disease, showed a good correlation with the inhibition results obtained for the plant (almond) enzyme. Surprisingly, although these compounds showed inhibition towards beta-glucocerebrosidase as acid hydrolase, they did not inhibit bovine liver beta-glucosidase as neutral hydrolase. In contrast to what was observed for beta-glucosidase inhibition, the coffee bean alpha-galactosidase inhibitors of the epimeric library (22b,k,p,r) only showed weak inhibition towards human lysosomal alpha-galactosidase. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.055

文献信息

• Structural basis of the inhibition of GH1 β-glucosidases by multivalent pyrrolidine iminosugars
  作者：Macarena Martínez-Bailén、Elena Jiménez-Ortega、Ana T. Carmona、Inmaculada Robina、Julia Sanz-Aparicio、David Talens-Perales、Julio Polaina、Camilla Matassini、Francesca Cardona、Antonio J. Moreno-Vargas

  DOI：10.1016/j.bioorg.2019.103026

  日期：2019.8

  The synthesis of multivalent pyrrolidine iminosugars via CuAAC click reaction between different pyrrolidine-azide derivatives and tri- or hexavalent alkynyl scaffolds is reported. The new multimeric compounds, together with the monomeric reference, were evaluated as inhibitors against two homologous GH1 β-glucosidases (BglA and BglB from Paenibacillus polymyxa). The multivalent inhibitors containing

  报道了通过不同的吡咯烷-叠氮化物衍生物与三价或六价炔基支架之间的CuAAC点击反应合成多价吡咯烷亚氨基糖。将新的多聚体化合物与单体参考物一起评估为针对两种同源GH1β-葡萄糖苷酶（多粘芽孢杆菌的BglA和BglB）的抑制剂。尽管两种酶的活性位点相似，但在吡咯烷和支架之间的接头中含有芳族部分的多价抑制剂可抑制八聚体BglA（μM范围），但对单体BglB没有亲和力。对六价抑制剂12检测到适度的多价效应（rp / n = 12）。对单体和三聚亚氨基糖抑制剂（4和10）与BglA之间的复合物进行结构分析，结果表明抑制剂在BglA的活性位点插入，证实了竞争性抑制作用，如酶动力学所示。另外，BglA / 4复合物与报道的BglB / 2F-葡萄糖复合物的结构比较说明了造成抑制作用的关键决定因素，并解释了抑制BglA和不抑制BglB的原因。根据这些观察结果，讨论了其他具有治疗意义的β-葡萄糖苷酶的潜在抑制作用。BglA
• Structure and temperature controlled synthesis of novel thiazolidin-4-one derivatives bearing an azasugar
  作者：Hua Chen、Sinan Wei、Hongbo Zhang、Xiaoliu Li

  DOI：10.1016/j.tetasy.2013.03.006

  日期：2013.4

  Novel thiazolidin-4-one linked pseudo-aza-disaccharides and thiazolidin-4-ones containing C-pseudo-aza-nucleosides were synthesized via a one-pot three component reaction. The former was synthesized stereoselectively by the tandem Staudinger/aza-Wittig/cyclization reaction of azasugar aldehyde 1, an azidosugar, and mercaptoacetic acid. The reaction was structure and temperature controlled, and could be

  通过一锅三组分反应合成了新型的噻唑烷酮-4-酮连接的伪氮杂二糖和含有C-伪氮杂核苷的噻唑烷-4-酮。前者是通过串联的Staudinger / aza-Wittig /氮杂糖醛1，叠氮基糖和巯基乙酸的环化反应立体合成的。该反应是结构和温度受控的，并且可以在40℃下立体定向地进行。这是噻唑烷定-4-酮连接衍生物的立体有择合成的首次报道。然而，这些衍生物是通过使杜鹃糖醛1，苯胺和巯基乙酸发生缩合反应而以低的立体选择性合成的。
• Exploring substituent diversity on pyrrolidine-aryltriazole iminosugars: Structural basis of β-glucocerebrosidase inhibition
  作者：Macarena Martínez-Bailén、Ana T. Carmona、Athéna C. Patterson-Orazem、Raquel L. Lieberman、Daisuke Ide、Moemi Kubo、Atsushi Kato、Inmaculada Robina、Antonio J. Moreno-Vargas

  DOI：10.1016/j.bioorg.2019.02.025

  日期：2019.5

  The synthesis of a library of pyrrolidine-aryltriazole hybrids through CuAAC between two epimeric dihydroxylated azidomethylpyrrolidines and differently substituted phenylacetylenes is reported. The evaluation of the new compounds as inhibitors of lysosomal β-glucocerebrosidase showed the importance of the substitution pattern of the phenyl moiety in the inhibition. Crystallization and docking studies

  报道了通过CuAAC在两个差向异构二羟基化叠氮基甲基吡咯烷与不同取代的苯基乙炔之间合成吡咯烷-芳基三唑杂合物的文库。对作为溶酶体β-葡萄糖脑苷脂酶抑制剂的新化合物的评估表明，在抑制作用中，苯基部分的取代方式很重要。结晶和对接研究揭示了吡咯烷基序与催化位点的氨基酸残基的关键相互作用，而芳基三唑部分沿疏水表面凹槽延伸。这些化合物中的某些能够增加Gaucher患者成纤维细胞中的酶活性，从而成为Gaucher疾病的新型化学分子伴侣。