(2S,3R,4R)-1-butyl-2-(hydroxymethyl)piperidine-3,4-diol | 1207673-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2S,3R,4R)-1-butyl-2-(hydroxymethyl)piperidine-3,4-diol
• CAS: 1207673-21-9
• 化学式: C₁₀H₂₁NO₃
• 分子量: 203.282
• InChiKey: IODUPADKAVXSTI-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2R,3S,4R)-1,3,4-tris(benzyloxy)hexane-2,5-diethylsulfonate 在 palladium 10% on activated carbon 、 氢气 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 20.0~90.0 ℃ 、506.66 kPa 条件下， 反应 48.0h， 生成 (2S,3R,4R)-1-butyl-2-(hydroxymethyl)piperidine-3,4-diol
  参考文献：
  名称：

  A concise synthesis of N-substituted fagomine derivatives and the systematic exploration of their α-glycosidase inhibition

  摘要：

  A novel and concise scheme has been developed successfully for the syntheses of N-substituted fagomine derivatives. The transformation of lactone (2) to 1,5-diol (3) was carried on with high yield (93-95%). The cyclization of 4 to 5 is a high stereoselective reaction (de value > 98%). It is disclosed that bulky substituent at N atom of the piperidine decreases the inhibition activity except those substituents having the ability of salvation or forming disulfide bond with M444 at the active site of alpha-glycosidase, which enhance the interaction with enzyme. Compounds with S-configuration at C-3 show greater activity than those with R-configuration. The structure activity relationship study is also supported by molecular docking analysis. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.004

文献信息

• A Fluorescence Polarization Activity-Based Protein Profiling Assay in the Discovery of Potent, Selective Inhibitors for Human Nonlysosomal Glucosylceramidase
  作者：Daniël Lahav、Bing Liu、Richard J. B. H. N. van den Berg、Adrianus M. C. H. van den Nieuwendijk、Tom Wennekes、Amar T. Ghisaidoobe、Imogen Breen、Maria J. Ferraz、Chi-Lin Kuo、Liang Wu、Paul P. Geurink、Huib Ovaa、Gijsbert A. van der Marel、Mario van der Stelt、Rolf G. Boot、Gideon J. Davies、Johannes M. F. G. Aerts、Herman S. Overkleeft

  DOI：10.1021/jacs.7b07352

  日期：2017.10.11

  assessed on GBA2 selectivity offset against the other glucosylceramide metabolizing enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA), and the cytosolic retaining β-glucosidase, GBA3. Our work, yielding potent and selective GBA2 inhibitors, also provides a roadmap for the development of high-throughput assays for identifying retaining glycosidase inhibitors by FluoPol-ABPP

  人非溶酶体葡萄糖基神经酰胺酶（GBA2）是控制糖脂水平的几种酶之一，其活性与几种人类疾病状态相关。迫切需要设计或发现选择性的GBA2抑制剂作为化学工具和潜在的治疗剂。在这里，我们描述了基于荧光偏振活性的蛋白质谱分析（FluoPol-ABPP）测定法的发展，该测定法可从350多种亚氨基糖文库中快速鉴定GBA2抑制剂。基于FluoPol-ABPP筛选的线索生成聚焦库，并针对与其他葡糖神经酰胺代谢酶，葡糖神经酰胺合酶（GCS），溶酶体葡糖神经酰胺酶（GBA）和胞质保留β-葡糖苷酶GBA3的GBA2选择性偏移进行评估。我们的工作产生了有效的和选择性的GBA2抑制剂，
• Assessment of Partially Deoxygenated Deoxynojirimycin Derivatives as Glucosylceramide Synthase Inhibitors
  作者：Richard J. B. H. N. van den Berg、Tom Wennekes、Amar Ghisaidoobe、Wilma E. Donker-Koopman、Anneke Strijland、Rolf G. Boot、Gijsbert A. van der Marel、Johannes M. F. G. Aerts、Herman S. Overkleeft

  DOI：10.1021/ml200050s

  日期：2011.7.14

  N-butyldeoxynojirimycin (Zavesca) is thought to inhibit through mimicry of its substrate, ceramide. In this work we demonstrate that, in contrast to what is proposed in this model, the C2-hydroxyl of the deoxynojirimycin core is important for GCS inhibition. Here we show that C6-OH appears of less important, which may set guidelines for the development of GCS inhibitors that have less affinity (in comparison with

  葡萄糖神经酰胺合酶 (GCS) 是一种已获批准的治疗戈谢病的药物靶点，被认为是对抗其他人类疾病（包括 2 型糖尿病）的有效靶点。临床药物N-丁基脱氧野尻霉素 (Zavesca) 被认为通过模拟其底物神经酰胺来抑制。在这项工作中，我们证明，与该模型中提出的相反，脱氧野尻霉素核心的 C2-羟基对于 GCS 抑制很重要。在这里，我们表明 C6-OH 似乎不那么重要，这可能为开发对其他糖加工酶（特别是作用于葡萄糖神经酰胺的水解酶）具有较低亲和力（与 Zavesca 相比）的 GCS 抑制剂制定指导方针。
• A concise synthesis of N-substituted fagomine derivatives and the systematic exploration of their α-glycosidase inhibition
  作者：Fu-xiang Jiang、Qiao-zhen Liu、Dan Zhao、Cui-ting Luo、Cui-ping Guo、Wen-cai Ye、Cheng Luo、Heru Chen

  DOI：10.1016/j.ejmech.2014.03.004

  日期：2014.4

  A novel and concise scheme has been developed successfully for the syntheses of N-substituted fagomine derivatives. The transformation of lactone (2) to 1,5-diol (3) was carried on with high yield (93-95%). The cyclization of 4 to 5 is a high stereoselective reaction (de value > 98%). It is disclosed that bulky substituent at N atom of the piperidine decreases the inhibition activity except those substituents having the ability of salvation or forming disulfide bond with M444 at the active site of alpha-glycosidase, which enhance the interaction with enzyme. Compounds with S-configuration at C-3 show greater activity than those with R-configuration. The structure activity relationship study is also supported by molecular docking analysis. (C) 2014 Elsevier Masson SAS. All rights reserved.