(1S,3aR,4S,8aS,9R)-decahydro-4,8,8-trimethyl-1,4-methanoazulen-9-carboxaldehyde | 66537-42-6

• 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
• 英文名称: (1S,3aR,4S,8aS,9R)-decahydro-4,8,8-trimethyl-1,4-methanoazulen-9-carboxaldehyde
• 英文别名: longifolyl aldehyde；(1S,6S,7R,10S,11R)-1,5,5-trimethyltricyclo[5.4.0.0^6,10]undecane-11-carbaldehyde；Longifolaldehyd；(1R,2S,7S,8R,9S)-3,3,7-trimethyltricyclo[5.4.0.02,9]undecane-8-carbaldehyde
• CAS: 66537-42-6
• 化学式: C₁₅H₂₄O
• 分子量: 220.355
• InChiKey: PBMHTGOFWRRJFS-NTASLKFISA-N

物化性质

• 沸点：
  286.7±9.0 °C(Predicted)
• 密度：
  1.015±0.06 g/cm3(Predicted)
• 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)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2912299000

反应信息

• 作为反应物：
  描述：

  氘代氯仿 、 (1S,3aR,4S,8aS,9R)-decahydro-4,8,8-trimethyl-1,4-methanoazulen-9-carboxaldehyde 生成 2,4,6-tris[(1S,3aR,4S,8aS,9S)-decahydro-4,8,8-trimethyl-1,4-methanoazulen-9-yl]-1,3,5-trioxane
  参考文献：
  名称：

  Longifolene的臭氧分解：一种制备有用的手性化合物的工具。NMR和X射线晶体学测定新立体中心的构型

  摘要：

  的臭氧分解（+） -长叶烯（1在不同溶剂（ET）2 O，CH 2氯2，氯仿3，丙酮）在-80℃提供定量长叶烯环氧化物（3），其为对映异构体的单，其中O型原子被内定位（方案2）。升温至室温后，环氧化物仅在丙酮中保持稳定，并以低熔点结晶化合物形式分离。在CH 2 Cl 2，Et 2 O或CHCl 3溶液中，环氧化物3迅速重排为异构烯醇4和5，进行了进一步的重排，得到了外醛6。在室温下于CH 2 Cl 2溶液中或在CHCl 3和Et 2 O中放置数周后，醛6缓慢重排为其差向异构体7。以制备规模分离出醛6和醛7，以用于进一步的合成用途。加入碘化甲基镁的至6和7中提供的相应的醇13 / 14和15 / 16分别分离为纯的非对映异构体（方案4）。新的手性中心在结构13 - 16通过NMR方法和X-射线晶体学测定。

  DOI：

  10.1002/hlca.200390000
• 作为产物：
  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

• The Ozonolysis of Longifolene: A Tool for the Preparation of Useful Chiral Compounds. Configuration Determination of New Stereogenic Centers by NMR Spectroscopy and X-Ray Crystallography
  作者：Vladimir Dimitrov、Gudrun Hopp Rentsch、Anthony Linden、Manfred Hesse

  DOI：10.1002/hlca.200390000

  日期：2003.1

  of methylmagnesium iodide to 6 and 7 provided the corresponding alcohols 13/14 and 15/16, respectively, which were isolated as pure diastereoisomers (Scheme 4). The configurations of the new chiral centers in 13–16 were determined by NMR methods and X-ray crystallography.

  的臭氧分解（+） -长叶烯（1在不同溶剂（ET）2 O，CH 2氯2，氯仿3，丙酮）在-80℃提供定量长叶烯环氧化物（3），其为对映异构体的单，其中O型原子被内定位（方案2）。升温至室温后，环氧化物仅在丙酮中保持稳定，并以低熔点结晶化合物形式分离。在CH 2 Cl 2，Et 2 O或CHCl 3溶液中，环氧化物3迅速重排为异构烯醇4和5，进行了进一步的重排，得到了外醛6。在室温下于CH 2 Cl 2溶液中或在CHCl 3和Et 2 O中放置数周后，醛6缓慢重排为其差向异构体7。以制备规模分离出醛6和醛7，以用于进一步的合成用途。加入碘化甲基镁的至6和7中提供的相应的醇13 / 14和15 / 16分别分离为纯的非对映异构体（方案4）。新的手性中心在结构13 - 16通过NMR方法和X-射线晶体学测定。
• 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.