(2E,6E,10E)-3,7-dimethyl-11-((tetrahydro-2H-pyran-2-yloxy)methyl)dodeca-2,6,10-trien-1-ol | 135896-11-6

• 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: (2E,6E,10E)-3,7-dimethyl-11-((tetrahydro-2H-pyran-2-yloxy)methyl)dodeca-2,6,10-trien-1-ol
• 英文别名: (2E,6E,10E)-3,7,11-trimethyl-12-((tetrahydro-2H-pyran-2-yl)oxy)dodeca-2,6,10-trien-1-ol；(2E,6E,10E)-3,7,11-trimethyl-12-(oxan-2-yloxy)dodeca-2,6,10-trien-1-ol
• CAS: 135896-11-6
• 化学式: C₂₀H₃₄O₃
• 分子量: 322.488
• InChiKey: FIPFQURFEUUGCK-ACQVSYCASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2E,6E,10E)-3,7-dimethyl-11-((tetrahydro-2H-pyran-2-yloxy)methyl)dodeca-2,6,10-trien-1-ol 在 溴 、 叔丁基锂 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-(tert-Butyl-dimethyl-silanyl)-3-[(2E,6E,10E)-3,7,11-trimethyl-12-(tetrahydro-pyran-2-yloxy)-dodeca-2,6,10-trienyl]-1H-indole
  参考文献：
  名称：

  Clark, J. Stephen; Myatt, James; Wilson, Claire, Chemical Communications, 2003, # 13, p. 1546 - 1547

  摘要：

  DOI：
• 作为产物：
  描述：

  反,反-西基乙酸 在 叔丁基过氧化氢 、 selenium(IV) oxide 、 4-甲基苯磺酸吡啶 、 水杨酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 37.0h， 生成 (2E,6E,10E)-3,7-dimethyl-11-((tetrahydro-2H-pyran-2-yloxy)methyl)dodeca-2,6,10-trien-1-ol
  参考文献：
  名称：

  探索GGTase-I底物要求。第2部分：新型饱和香叶基香叶基二磷酸类似物的合成及生化分析

  摘要：

  蛋白质异戊二烯化是一种翻译后修饰，可帮助某些蛋白质定位于血浆中的成员，并在这些成员中激活细胞信号传导。为了更好地了解类异戊二烯的需求和FTase和GGTase-I的差异，合成了一系列饱和的香叶基香叶基二磷酸二氢类似物，并针对哺乳动物FTase和GGTase-I进行了筛选。在我们的化合物库中，几种类似物被证明是GGTase-I的底物，与 GGPP（k rel  = 1.0）相比，11d的k rel = 0.95 。

  DOI：

  10.1016/j.bmcl.2016.06.035

文献信息

• Design and synthesis of biologically active analogues of vitamin K2: Evaluation of their biological activities with cultured human cell lines
  作者：Yoshitomo Suhara、Yoshihisa Hirota、Kimie Nakagawa、Maya Kamao、Naoko Tsugawa、Toshio Okano

  DOI：10.1016/j.bmc.2007.12.025

  日期：2008.3.15

  Novel omega-oxygenated vitamin K(2) analogues were efficiently synthesized and their biological activities were evaluated. Some were biologically active and the side-chain played an important role in gamma-carboxylation and apoptosis-inducing activity. The results provide useful information on the structure-activity relationship of vitamin K(2) analogues for the development of new drugs.

  新型的ω-氧化的维生素K（2）类似物被有效地合成，并对其生物学活性进行了评估。一些具有生物活性，并且侧链在γ-羧化和诱导细胞凋亡的活性中起重要作用。结果提供了有关维生素K（2）类似物的结构-活性关系的新药开发有用的信息。
• Synthetic Small Molecules Derived from Natural Vitamin K Homologues that Induce Selective Neuronal Differentiation of Neuronal Progenitor Cells
  作者：Yoshitomo Suhara、Yoshihisa Hirota、Norika Hanada、Shun Nishina、Sachiko Eguchi、Rie Sakane、Kimie Nakagawa、Akimori Wada、Kazuhiko Takahashi、Hiroaki Tokiwa、Toshio Okano

  DOI：10.1021/acs.jmedchem.5b00999

  日期：2015.9.10

  We synthesized new vitamin K2 analogues with ω-terminal modifications of the side chain and evaluated their selective differentiation of neuronal progenitor cells into neurons in vitro. The result of the assay showed that the menaquinone-3 analogue modified with the m-methylphenyl group had the most potent activity, which was twice as great as the control. This finding indicated that it is possible

  我们合成了具有侧链ω-末端修饰的新型维生素K 2类似物，并评估了它们在体外将神经元祖细胞选择性分化为神经元的能力。该测定的结果表明，甲基萘醌-3类似物与改性米甲基苯基组具有最有效的活性，这是两倍大的控制。该发现表明，可以通过改变维生素K 2的结构获得更有效的化合物。
• Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities
  作者：Rie Sakane、Kimito Kimura、Yoshihisa Hirota、Michiyasu Ishizawa、Yuta Takagi、Akimori Wada、Shigefumi Kuwahara、Makoto Makishima、Yoshitomo Suhara

  DOI：10.1016/j.bmcl.2017.09.038

  日期：2017.11

  for steroid and xenobiotic receptors, protection of neuronal cells from oxidative stress, and so on. From this background, we focused on the role of menaquinone in the differentiation activity of progenitor cells into neuronal cells and we synthesized novel vitamin K derivatives with modification of the ω-terminal side chain. We report here new vitamin K analogues, which introduced an alkylated phenyl

  维生素K是γ-谷氨酰羧化酶必不可少的辅助因子，与凝血和骨形成有关。Menaquinone-4是维生素K的同系物之一，是在体内生物合成的，具有多种生物活性，例如是甾体和异种生物受体的配体，保护神经元细胞免受氧化应激等。从这一背景出发，我们集中研究了甲萘醌在祖细胞向神经元细胞分化中的作用，并合成了具有ω-末端侧链修饰的新型维生素K衍生物。我们在这里报告了新的维生素K类似物，它在ω-末端侧链上引入了烷基化的苯基。与对照相比，这些化合物表现出有效的分化活性。
• Synthesis of Novel Vitamin K₂ Analogues with Modification at the ω-Terminal Position and Their Biological Evaluation as Potent Steroid and Xenobiotic Receptor (SXR) Agonists
  作者：Yoshitomo Suhara、Masato Watanabe、Kimie Nakagawa、Akimori Wada、Yoichi Ito、Kazuyoshi Takeda、Kazuhiko Takahashi、Toshio Okano

  DOI：10.1021/jm200025f

  日期：2011.6.23

  Vitamin K-2 is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized vitamin K-2 analogues with hydroxyl or phenyl groups at the omega-terminal of the side chain. The up-regulation of SXR-mediated transcription of the target gene by the analogues was dependent on the length of the side chain and the hydrophobicity of the omega-terminal residues. Phenyl analogue menaquinone-3 was as active as the known SXR ligand rifampicin.
• Efficient synthesis and biological evaluation of ω-oxygenated analogues of vitamin K2: Study of modification and structure–activity relationship of vitamin K2 metabolites
  作者：Yoshitomo Suhara、Aya Murakami、Maya Kamao、Shino Mimatsu、Kimie Nakagawa、Naoko Tsugawa、Toshio Okano

  DOI：10.1016/j.bmcl.2006.12.082

  日期：2007.3

  Novel omega-oxygenated vitamin K-2 analogues, which are candidates for metabolites of vitamin K-2 homologues, were efficiently synthesized and their apoptosis-inducing activity was evaluated. We revealed that some of those analogues were biologically active and the side-chain part played an important role in apoptosis-inducing activity. Our results can provide useful information to develop the structure-activity relationship of vitamin K-2 analogues for new drugs based on vitamin K. (c) 2007 Elsevier Ltd. All rights reserved.