N-(((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-methylpyrrolidin-2-yl)methyl)acetamide | 306297-21-2

• 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: N-(((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-methylpyrrolidin-2-yl)methyl)acetamide
• 英文别名: N-[[(2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-methylpyrrolidin-2-yl]methyl]acetamide
• CAS: 306297-21-2
• 化学式: C₉H₁₈N₂O₄
• 分子量: 218.253
• InChiKey: GUYSAAUIAYZIMA-JQCXWYLXSA-N

物化性质

• 沸点：
  479.1±28.0 °C(Predicted)
• 密度：
  1.266±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  93
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-methylpyrrolidin-2-yl)methyl)acetamide 、 叔丁基二甲硅基三氟甲磺酸酯 在 三乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 1.0h， 以90%的产率得到N-(((2S,3R,4R,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3,4-dihydroxy-1-methylpyrrolidin-2-yl)methyl)acetamide
  参考文献：
  名称：

  Iminocyclitol inhibitors of hexoaminidase and glycosidase

  摘要：

  披露了设计的亚氨基糖醇，它们对己糖苷酶和苷具有强大的抑制活性。

  公开号：

  US06774140B1
• 作为产物：
  描述：

  C-((2S,3R,4R,5R)-3,4-Bis-benzyloxy-5-benzyloxymethyl-1-methyl-pyrrolidin-2-yl)-methylamine 在 palladium on activated charcoal 吡啶 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 N-(((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-methylpyrrolidin-2-yl)methyl)acetamide
  参考文献：
  名称：

  Synthesis and High-Throughput Screening of N-Acetyl-β-hexosaminidase Inhibitor Libraries Targeting Osteoarthritis

  摘要：

  C1 Nitrogen iminocyclitols are potent inhibitors of N-acetyl-beta-hexosaminidases. Given hexosaminidases' important roles in osteoarthritis, we developed two straightforward and efficient syntheses of C1 nitrogen iminocyclitols from two readily available starting materials, D-mannosamine hydrochloride and the microbial oxidation product of fructose. A diversity-oriented synthetic strategy was then performed by coupling these core structures with various aldehydes, carboxylic acids, and alkynes to generate three separate libraries. High-throughput screening of the generated libraries with human N-acetyl-beta-hexosaminidases produced only moderate inhibitory activities. However, the synthetic approach and screening strategy for these compounds will be applied to develop new potent inhibitors of human N-acetyl-beta-hexosaminidases, particularly when combined with the structural information of these enzymes.

  DOI：

  10.1021/jo049355h

文献信息

• Iminocyclitol inhibitors of hexoaminidase and glycosidase
  申请人：The Scripps Research Institute

  公开号：US06774140B1

  公开（公告）日：2004-08-10

  Designed iminocylitols that have potent inhibition activity with respect to hexominidases and glycosides are disclosed.

  披露了设计的亚氨基糖醇，它们对己糖苷酶和苷具有强大的抑制活性。
• Synthesis and High-Throughput Screening of <i>N</i>-Acetyl-β-hexosaminidase Inhibitor Libraries Targeting Osteoarthritis
  作者：Junjie Liu、Mehdi M. D. Numa、Haitian Liu、Shi-Jung Huang、Pamela Sears、Alexander R. Shikhman、Chi-Huey Wong

  DOI：10.1021/jo049355h

  日期：2004.9.1

  C1 Nitrogen iminocyclitols are potent inhibitors of N-acetyl-beta-hexosaminidases. Given hexosaminidases' important roles in osteoarthritis, we developed two straightforward and efficient syntheses of C1 nitrogen iminocyclitols from two readily available starting materials, D-mannosamine hydrochloride and the microbial oxidation product of fructose. A diversity-oriented synthetic strategy was then performed by coupling these core structures with various aldehydes, carboxylic acids, and alkynes to generate three separate libraries. High-throughput screening of the generated libraries with human N-acetyl-beta-hexosaminidases produced only moderate inhibitory activities. However, the synthetic approach and screening strategy for these compounds will be applied to develop new potent inhibitors of human N-acetyl-beta-hexosaminidases, particularly when combined with the structural information of these enzymes.