[1S-(1alpha,3abeta,4alpha,8abeta,9S*)]-十氢-4,8,8-三甲基-1,4-甲桥薁-9-甲醇 | 469-27-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: [1S-(1alpha,3abeta,4alpha,8abeta,9S*)]-十氢-4,8,8-三甲基-1,4-甲桥薁-9-甲醇
• 英文名称: Longifolol
• 英文别名: [(1R,2S,7S,8R,9S)-3,3,7-trimethyl-8-tricyclo[5.4.0.02,9]undecanyl]methanol
• CAS: 469-27-2
• 化学式: C₁₅H₂₆O
• 分子量: 222.371
• InChiKey: VZJHQHUOVIDRCF-NTASLKFISA-N

物化性质

• 溶解度：
  溶于氯仿、二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  [1S-(1alpha,3abeta,4alpha,8abeta,9S*)]-十氢-4,8,8-三甲基-1,4-甲桥薁-9-甲醇 在 2-碘酰基苯甲酸 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 以100%的产率得到(1S,3aR,4S,8aS,9R)-decahydro-4,8,8-trimethyl-1,4-methanoazulen-9-carboxaldehyde
  参考文献：
  名称：

  Eudismic analysis of tricyclic sesquiterpenoid alcohols: Lead structures for the design of potent inhibitors of the human UDP-glucuronosyltransferase 2B7

  摘要：

  The epimeric tricyclic sesquiterpenoid alcohols globulol, epiglobulol, cedrol, epicedrol, longifolol, and isolongifolol were investigated in their ability to inhibit the recombinant human UDP-glucuronosyltransferase (UGT) 2B7. The stereoisomers displayed rapidly reversible competitive inhibition, which was substrate-independent. Longifolol and its stereoisomer isolongifolol displayed the lowest competitive inhibition constants (K-ic) of 23 and 26 nM, respectively. The K-ic values of cedrol and its epimer epicedrol were 0.15 and 0.21 mu M, those of globulol and epiglobulol were 5.4 and 4.0 mu M, respectively. The diastereomeric alcohols exhibited nearly identical affinities toward UGT2B7 indicating that the spatial arrangement of the hydroxy group had no influence on the dissociation of the enzyme-terpenoid complex. The high affinities stemmed presumably from mere hydrophobic interactions between the hydrocarbon scaffold of the terpenoid alcohol and the binding site of the enzyme. Glucuronidation assays revealed that there were large differences in the rates at which the epimeric alcohols were conjugated. Therefore, the spatial arrangement of the hydroxy group controlled the rate of the UGT2B7-catalyzed reaction. The introduction of a methyl group into the side chain of isolongifolol and longifolol increased the steric hindrance. As a result, the rate of the UGT2B7-catalyzed reaction was decreased by more than 88%. The findings indicated that the rate of the UGT2B7-catalyzed glucuronidation is significantly controlled by stereochemical and steric factors. Considering the high inhibition levels exerted by the tricyclic sesquiterpenoid alcohols, these compounds might serve as valuable lead structures for the design of potent inhibitors for UGT2B7. (c) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2007.07.002

文献信息

• Arantes, Simone Fontes; Hanson, James R.; Hitchcock, Peter B., Journal of Chemical Research, Miniprint, 2003, # 9, p. 959 - 971
  作者：Arantes, Simone Fontes、Hanson, James R.、Hitchcock, Peter B.

  DOI：——

  日期：——
• Eudismic analysis of tricyclic sesquiterpenoid alcohols: Lead structures for the design of potent inhibitors of the human UDP-glucuronosyltransferase 2B7
  作者：Ingo Bichlmaier、Mika Kurkela、Antti Siiskonen、Moshe Finel、Jari Yli-Kauhaluoma

  DOI：10.1016/j.bioorg.2007.07.002

  日期：2007.10

  The epimeric tricyclic sesquiterpenoid alcohols globulol, epiglobulol, cedrol, epicedrol, longifolol, and isolongifolol were investigated in their ability to inhibit the recombinant human UDP-glucuronosyltransferase (UGT) 2B7. The stereoisomers displayed rapidly reversible competitive inhibition, which was substrate-independent. Longifolol and its stereoisomer isolongifolol displayed the lowest competitive inhibition constants (K-ic) of 23 and 26 nM, respectively. The K-ic values of cedrol and its epimer epicedrol were 0.15 and 0.21 mu M, those of globulol and epiglobulol were 5.4 and 4.0 mu M, respectively. The diastereomeric alcohols exhibited nearly identical affinities toward UGT2B7 indicating that the spatial arrangement of the hydroxy group had no influence on the dissociation of the enzyme-terpenoid complex. The high affinities stemmed presumably from mere hydrophobic interactions between the hydrocarbon scaffold of the terpenoid alcohol and the binding site of the enzyme. Glucuronidation assays revealed that there were large differences in the rates at which the epimeric alcohols were conjugated. Therefore, the spatial arrangement of the hydroxy group controlled the rate of the UGT2B7-catalyzed reaction. The introduction of a methyl group into the side chain of isolongifolol and longifolol increased the steric hindrance. As a result, the rate of the UGT2B7-catalyzed reaction was decreased by more than 88%. The findings indicated that the rate of the UGT2B7-catalyzed glucuronidation is significantly controlled by stereochemical and steric factors. Considering the high inhibition levels exerted by the tricyclic sesquiterpenoid alcohols, these compounds might serve as valuable lead structures for the design of potent inhibitors for UGT2B7. (c) 2007 Elsevier Inc. All rights reserved.