phenyl 3,4,6-tri-O-acetyl-2-C-(carboxymethyl-N-benzyloxyamide)-2-deoxy-1-thio-D-glucopyranoside | 1363730-87-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: phenyl 3,4,6-tri-O-acetyl-2-C-(carboxymethyl-N-benzyloxyamide)-2-deoxy-1-thio-D-glucopyranoside
• CAS: 1363730-87-3
• 化学式: C₂₇H₃₁NO₉S
• 分子量: 545.61
• InChiKey: ACYUMNIYMSEEDD-IYYUPZBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.18
• 重原子数：
  38.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  126.46
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  二碳酸二叔丁酯 、 phenyl 3,4,6-tri-O-acetyl-2-C-(carboxymethyl-N-benzyloxyamide)-2-deoxy-1-thio-D-glucopyranoside 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 phenyl 3,4,6-tri-O-acetyl-2-C-(carboxymethyl-N-tert-butyloxycarbonyl-N-benzyloxy-amide)-2-deoxy-D-glucopyranoside 、 phenyl 3,4,6-tri-O-acetyl-2-C-(carboxymethyl-N-tert-butyloxycarbonyl-N-benzyloxy-amide)-2-deoxy-D-glucopyranoside
  参考文献：
  名称：

  Inhibitors Incorporating Zinc‐Binding Groups Target the GlcNAc‐PI de‐N‐acetylase inTrypanosoma brucei, the Causative Agent of African Sleeping Sickness

  摘要：

  Disruption of glycosylphosphatidylinositol biosynthesis is genetically and chemically validated as a drug target against the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. The N‐acetylglucosamine‐phosphatidylinositol de‐N‐acetylase (deNAc) is a zinc metalloenzyme responsible for the second step of glycosylphosphatidylinositol biosynthesis. We recently reported the synthesis of eight deoxy‐2‐C‐branched monosaccharides containing carboxylic acid, hydroxamic acid, or N‐hydroxyurea substituents at the C2 position that may act as zinc‐binding groups. Here, we describe the synthesis of a glucocyclitol‐phospholipid incorporating a hydroxamic acid moiety and report the biochemical evaluation of the monosaccharides and the glucocyclitol‐phospholipid as inhibitors of the trypanosome deNAc in the cell‐free system and against recombinant enzyme. Monosaccharides with carboxylic acid or hydroxamic acid substituents were found to be the inhibitors of the trypanosome deNAc with IC50 values 0.1–1.5 mm, and the glucocyclitol‐phospholipid was found to be a dual inhibitor of the deNAc and the α1‐4‐mannose transferase with an apparent IC50 = 19 ± 0.5 μm.

  DOI：

  10.1111/j.1747-0285.2011.01300.x
• 作为产物：
  描述：

  2-((3R,4R,5S,6R)-4,5-diacetoxy-6-(acetoxymethyl)-2-(phenylthio)tetrahydro-2H-pyran-3-yl)acetic acid 、 苄氧基胺盐酸盐 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以80%的产率得到phenyl 3,4,6-tri-O-acetyl-2-C-(carboxymethyl-N-benzyloxyamide)-2-deoxy-1-thio-D-glucopyranoside
  参考文献：
  名称：

  Inhibitors Incorporating Zinc‐Binding Groups Target the GlcNAc‐PI de‐N‐acetylase inTrypanosoma brucei, the Causative Agent of African Sleeping Sickness

  摘要：

  Disruption of glycosylphosphatidylinositol biosynthesis is genetically and chemically validated as a drug target against the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. The N‐acetylglucosamine‐phosphatidylinositol de‐N‐acetylase (deNAc) is a zinc metalloenzyme responsible for the second step of glycosylphosphatidylinositol biosynthesis. We recently reported the synthesis of eight deoxy‐2‐C‐branched monosaccharides containing carboxylic acid, hydroxamic acid, or N‐hydroxyurea substituents at the C2 position that may act as zinc‐binding groups. Here, we describe the synthesis of a glucocyclitol‐phospholipid incorporating a hydroxamic acid moiety and report the biochemical evaluation of the monosaccharides and the glucocyclitol‐phospholipid as inhibitors of the trypanosome deNAc in the cell‐free system and against recombinant enzyme. Monosaccharides with carboxylic acid or hydroxamic acid substituents were found to be the inhibitors of the trypanosome deNAc with IC50 values 0.1–1.5 mm, and the glucocyclitol‐phospholipid was found to be a dual inhibitor of the deNAc and the α1‐4‐mannose transferase with an apparent IC50 = 19 ± 0.5 μm.

  DOI：

  10.1111/j.1747-0285.2011.01300.x