(R)-3,5-dimethyl-4-hydroxy-5-(4-hydroxy-2-methylbutyl)-5H-thiophen-2-one | 873801-64-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-3,5-dimethyl-4-hydroxy-5-(4-hydroxy-2-methylbutyl)-5H-thiophen-2-one
• 英文别名: (5R)-4-hydroxy-5-(4-hydroxy-2-methylbutyl)-3,5-dimethylthiophen-2-one
• CAS: 873801-64-0
• 化学式: C₁₁H₁₈O₃S
• 分子量: 230.328
• InChiKey: GJLCPJUODZJNCV-PLNQYNMKSA-N

物化性质

• 沸点：
  370.0±42.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  82.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-3,5-dimethyl-4-hydroxy-5-(4-hydroxy-2-methylbutyl)-5H-thiophen-2-one 在 potassium tert-butylate 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 7.5h， 生成 (R)-4-Hydroxy-3,5-dimethyl-5-(2-methyl-but-3-enyl)-5H-thiophen-2-one
  参考文献：
  名称：

  Structure−Activity Relationships at the 5-Position of Thiolactomycin:  An Intact (5R)-Isoprene Unit Is Required for Activity against the Condensing Enzymes from Mycobacterium tuberculosis and Escherichia coli

  摘要：

  Thiolactomycin inhibits bacterial cell growth through inhibition of the beta-ketoacyl-ACP synthase activity of type II fatty acid synthases. The effect of modifications of the 5-position isoprenoid side chain on both IC(50) and MIC were determined. Synthesis and screening of a structurally diverse set of 5-position analogues revealed very little tolerance for substitution in purified enzyme assays, but a few analogues retained MIC, presumably through another target. Even subtle modifications such as reducing one or both double bonds of the diene were not tolerated. The only permissible structural modifications were removal of the isoprene methyl group or addition of a methyl group to the terminus. Cocrystallization of these two inhibitors with the condensing enzyme from Escherichia coli revealed that they retained the TLM binding mode at the active site with reduced affinity. These results suggest a strict requirement for a conjugated, planar side chain inserting within the condensing enzyme active site.

  DOI：

  10.1021/jm050825p
• 作为产物：
  描述：

  乳霉素 在 9-borabicyclo[3.3.1]nonane dimer 、 双氧水 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 8.17h， 生成 (R)-3,5-dimethyl-4-hydroxy-5-(4-hydroxy-2-methylbutyl)-5H-thiophen-2-one
  参考文献：
  名称：

  Structure−Activity Relationships at the 5-Position of Thiolactomycin:  An Intact (5R)-Isoprene Unit Is Required for Activity against the Condensing Enzymes from Mycobacterium tuberculosis and Escherichia coli

  摘要：

  Thiolactomycin inhibits bacterial cell growth through inhibition of the beta-ketoacyl-ACP synthase activity of type II fatty acid synthases. The effect of modifications of the 5-position isoprenoid side chain on both IC(50) and MIC were determined. Synthesis and screening of a structurally diverse set of 5-position analogues revealed very little tolerance for substitution in purified enzyme assays, but a few analogues retained MIC, presumably through another target. Even subtle modifications such as reducing one or both double bonds of the diene were not tolerated. The only permissible structural modifications were removal of the isoprene methyl group or addition of a methyl group to the terminus. Cocrystallization of these two inhibitors with the condensing enzyme from Escherichia coli revealed that they retained the TLM binding mode at the active site with reduced affinity. These results suggest a strict requirement for a conjugated, planar side chain inserting within the condensing enzyme active site.

  DOI：

  10.1021/jm050825p