p-methylphenyl 3,4,6-tri-O-benzyl-2-deoxy-2-azido-1-thio-D-mannopyranoside | 765308-76-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: p-methylphenyl 3,4,6-tri-O-benzyl-2-deoxy-2-azido-1-thio-D-mannopyranoside
• 英文别名: (2R,3S,4R,5S,6R)-3-azido-2-(4-methylphenyl)sulfanyl-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxane
• CAS: 765308-76-7
• 化学式: C₃₄H₃₅N₃O₄S
• 分子量: 581.736
• InChiKey: LPLQEOSOGHPWID-KKYNAJBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  p-methylphenyl 3,4,6-tri-O-benzyl-2-deoxy-2-azido-1-thio-D-mannopyranoside 在 N-碘代丁二酰亚胺 作用下， 以 水 、 丙酮 为溶剂， 反应 3.0h， 以65%的产率得到2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-mannopyranose
  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-azido-2-deoxy-D-mannopyranose 在 吡啶 、 三氟化硼乙醚 、 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 p-methylphenyl 3,4,6-tri-O-benzyl-2-deoxy-2-azido-1-thio-D-mannopyranoside
  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.