N-((4R,5S,6S)-4-(benzylthio)-5,6-dihydroxy-3-oxocyclohex-1-en-1-yl)-2-hydroxybenzamide | 1059670-12-0

• 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: N-((4R,5S,6S)-4-(benzylthio)-5,6-dihydroxy-3-oxocyclohex-1-en-1-yl)-2-hydroxybenzamide
• CAS: 1059670-12-0
• 化学式: C₂₀H₁₉NO₅S
• 分子量: 385.441
• InChiKey: ITOGUEPZPVKQSA-FHWLQOOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.61
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  106.86
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-((4R,5S,6S)-4-(benzylthio)-5,6-dihydroxy-3-oxocyclohex-1-en-1-yl)-2-hydroxybenzamide 在 盐酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以43%的产率得到
  参考文献：
  名称：

  Inactivation of NF-κB Components by Covalent Binding of (−)-Dehydroxymethylepoxyquinomicin to Specific Cysteine Residues

  摘要：

  Previously, we designed and synthesized a potent NF-kappa B inhibitor, DHMEQ. Although DHMEQ showed potent anti-inflammatory and anticancer activities in animals, its molecular target has not been elucidated. In the present study, its target protein was found to be p65 and other Rel homology proteins. We found that (-)-DHMEQ bound to p65 covalently with a 1: 1 stoichiometry by conducting SPR and MALDI-TOF MS analyses. MS analysis of the chymotrypsin-digested peptide suggested the binding of (-)-DHMEQ to a Cys residue. Formation of Cys/(-)-DHMEQ adduct in the protein was supported by chemical synthesis of the adduct. Substitution of specific Cys in p65 and other Rel homology proteins resulted in the loss of (-)-DHMEQ binding. (-)-DHMEQ is the first NF-kappa B inhibitor that was proven to bind to the specific Cys by chemical methodology. These findings may explain the highly selective inhibition of NF-kappa B and the low toxic effect of (-)-DHMEQ in cells and animals.

  DOI：

  10.1021/jm8006245
• 作为产物：
  描述：

  苄硫醇 、 (-)-2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以89%的产率得到N-((4R,5S,6S)-4-(benzylthio)-5,6-dihydroxy-3-oxocyclohex-1-en-1-yl)-2-hydroxybenzamide
  参考文献：
  名称：

  Inactivation of NF-κB Components by Covalent Binding of (−)-Dehydroxymethylepoxyquinomicin to Specific Cysteine Residues

  摘要：

  Previously, we designed and synthesized a potent NF-kappa B inhibitor, DHMEQ. Although DHMEQ showed potent anti-inflammatory and anticancer activities in animals, its molecular target has not been elucidated. In the present study, its target protein was found to be p65 and other Rel homology proteins. We found that (-)-DHMEQ bound to p65 covalently with a 1: 1 stoichiometry by conducting SPR and MALDI-TOF MS analyses. MS analysis of the chymotrypsin-digested peptide suggested the binding of (-)-DHMEQ to a Cys residue. Formation of Cys/(-)-DHMEQ adduct in the protein was supported by chemical synthesis of the adduct. Substitution of specific Cys in p65 and other Rel homology proteins resulted in the loss of (-)-DHMEQ binding. (-)-DHMEQ is the first NF-kappa B inhibitor that was proven to bind to the specific Cys by chemical methodology. These findings may explain the highly selective inhibition of NF-kappa B and the low toxic effect of (-)-DHMEQ in cells and animals.

  DOI：

  10.1021/jm8006245

文献信息

• Unusual intramolecular N→O acyl group migration occurring during conjugation of (−)-DHMEQ with cysteine
  作者：Ikuko Kozawa、Kuniki Kato、Toshiaki Teruya、Kiyotake Suenaga、Kazuo Umezawa

  DOI：10.1016/j.bmcl.2009.07.123

  日期：2009.9

  covalently bound to a specific cysteine of NF-κB component proteins. In the course of formation of the (−)-DHMEQ and protected cysteine conjugate, we observed an unusual intramolecular N→O acyl group migration.

  以前，我们发现（-）-DHMEQ，一种特定的NF-κB抑制剂，与特定的NF-κB组分半胱氨酸共价结合。在（-）-DHMEQ和受保护的半胱氨酸缀合物形成过程中，我们观察到了异常的分子内N → O酰基迁移。