(2R,3R,4R,5R)-2-(tert-butyl-dimethyl-sylanyloxy-methyl)-3,4-di-O-benzyl-5-(O-benzyl-methyl)-pyrrolidine | 765308-80-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,3R,4R,5R)-2-(tert-butyl-dimethyl-sylanyloxy-methyl)-3,4-di-O-benzyl-5-(O-benzyl-methyl)-pyrrolidine
• 英文别名: [(2R,3R,4R,5R)-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)pyrrolidin-2-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 765308-80-3
• 化学式: C₃₃H₄₅NO₄Si
• 分子量: 547.81
• InChiKey: VJEZIWDDMJPJQO-SEVDZJIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.74
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-2-(tert-butyl-dimethyl-sylanyloxy-methyl)-3,4-di-O-benzyl-5-(O-benzyl-methyl)-pyrrolidine 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (2R,3R,4R,5R)-N-butyloxycarbonyl-3,4-bis(benzyloxy)-5-<(benzyloxy)methyl>-2-(hydroxymethyl)pyrrolidine
  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
• 作为产物：
  描述：

  2-deoxy-2-azido-3,4,6-tri-O-benzyl-D-mannitol 在 palladium on activated charcoal 吡啶 、 氢气 、 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 (2R,3R,4R,5R)-2-(tert-butyl-dimethyl-sylanyloxy-methyl)-3,4-di-O-benzyl-5-(O-benzyl-methyl)-pyrrolidine
  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

• 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.