3,3,7-三甲基三环[5.4.0.02,9]十一烷-8-甲醛 | 25491-00-3

• 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: 3,3,7-三甲基三环[5.4.0.02,9]十一烷-8-甲醛
• 英文名称: (1R,2S,7S,8S,9S)-3,3,7-trimethyltricyclo[5.4.0.0^2,9]undecane-8-carbaldehyde
• 英文别名: (1S,3aR,4S,8aS,9S)-decahydro-4,8,8-trimethyl-1,4-methanoazulen-9-carboxaldehyde；isolongifolyl aldehyde；longifolen aldehyde；(1S,6S,7R,10S,11S)-1,5,5-trimethyltricyclo[5.4.0.0^6,10]undecane-11-carbaldehyde；7βH-Longifol-15-aldehyd；Isolongifolal；(1R,2S,7S,8S,9S)-3,3,7-trimethyltricyclo[5.4.0.02,9]undecane-8-carbaldehyde
• CAS: 25491-00-3
• 化学式: C₁₅H₂₄O
• 分子量: 220.355
• InChiKey: PBMHTGOFWRRJFS-BIGJJFBESA-N

物化性质

• 沸点：
  150-160 °C(Press: 3 Torr)
• 密度：
  1.015±0.06 g/cm3(Predicted)

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

反应信息

• 作为反应物：
  描述：

  3,3,7-三甲基三环[5.4.0.02,9]十一烷-8-甲醛 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 diisopropyl {2-[(1R,2S,7S,8S,9S)-3,3,7-trimethyltricyclo[5.4.0.0^2,9]undec-8-yl]ethyl}phosphonate
  参考文献：
  名称：

  异longifolol衍生物对人UDP-葡萄糖醛酸转移酶2B7的同工型选择性抑制。

  摘要：

  合成了一组48个三环倍半萜醇异长叶醇的衍生物。该组包括高手性和非对映异构的醇，胺，氯代醇，以及羧酸，膦酸及其相应的酯。差向异构化合物的绝对构型由2D NMR实验[梯度异核单量子相关性（gHSQC）和梯度核Overhauser增强光谱法（gNOESY）]分配，与晶体学数据一致。三环衍生物被评估为人类UDP-葡萄糖醛酸糖基转移酶（UGT）2B7的抑制剂。苯基取代的仲醇26b是该系列中最好的抑制剂，其竞争抑制常数为18 nM。化合物26b没有被UGT2B7和其他肝脏UGT酶葡萄糖醛酸化，大概是由于其庞大的苯基取代基所造成的高位阻。确定了其对亚家族1A和2B的另外14种UGT同工型的抑制活性，并且数据表明三环仲醇26b对UGT2B7具有高度选择性（真实选择性> 1000）。

  DOI：

  10.1021/jm061204e
• 作为产物：
  描述：

  (-)-异长叶醇 在 吡啶 、 chromium(VI) oxide 作用下， 生成 3,3,7-三甲基三环[5.4.0.02,9]十一烷-8-甲醛
  参考文献：
  名称：

  倍半萜的研究-XXXVI：-长叶酸的结构

  摘要：

  明确表明，长叶烯的铬酸氧化产物ψ-长叶酸具有结构V.

  DOI：

  10.1016/0040-4020(68)88173-6

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。
• Studies in sesquiterpenes—XXXVI
  作者：G. Mehta、N.R. Nayak、Sukh Dev

  DOI：10.1016/0040-4020(68)88173-6

  日期：1968.1

  ψ-Longifolic acid, a chromic acid oxidation product of longifolene, is unequivocally shown to possess the structure V.

  明确表明，长叶烯的铬酸氧化产物ψ-长叶酸具有结构V.
• 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.
• Helmlinger,D.; Ourisson,G., Justus Liebigs Annalen der Chemie, 1965, vol. 686, p. 19 - 33
  作者：Helmlinger,D.、Ourisson,G.

  DOI：——

  日期：——
• Isoform-Selective Inhibition of the Human UDP-glucuronosyltransferase 2B7 by Isolongifolol Derivatives
  作者：Ingo Bichlmaier、Mika Kurkela、Tanmaya Joshi、Antti Siiskonen、Tobias Rüffer、Heinrich Lang、Bohumila Suchanová、Mikko Vahermo、Moshe Finel、Jari Yli-Kauhaluoma

  DOI：10.1021/jm061204e

  日期：2007.5.1

  crystallographic data. The tricyclic derivatives were assessed as inhibitors of the human UDP-glucuronosyltransferase (UGT) 2B7. The phenyl-substituted secondary alcohol 26b was the best inhibitor in this series and its competitive inhibition constant was 18 nM. Compound 26b was not glucuronidated by UGT2B7 and other hepatic UGT enzymes, presumably due to the high steric hindrance exerted by its bulky phenyl

  合成了一组48个三环倍半萜醇异长叶醇的衍生物。该组包括高手性和非对映异构的醇，胺，氯代醇，以及羧酸，膦酸及其相应的酯。差向异构化合物的绝对构型由2D NMR实验[梯度异核单量子相关性（gHSQC）和梯度核Overhauser增强光谱法（gNOESY）]分配，与晶体学数据一致。三环衍生物被评估为人类UDP-葡萄糖醛酸糖基转移酶（UGT）2B7的抑制剂。苯基取代的仲醇26b是该系列中最好的抑制剂，其竞争抑制常数为18 nM。化合物26b没有被UGT2B7和其他肝脏UGT酶葡萄糖醛酸化，大概是由于其庞大的苯基取代基所造成的高位阻。确定了其对亚家族1A和2B的另外14种UGT同工型的抑制活性，并且数据表明三环仲醇26b对UGT2B7具有高度选择性（真实选择性> 1000）。