omega-Hydroxymenaquinone-4 | 934831-09-1

• 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: omega-Hydroxymenaquinone-4
• 英文别名: 2-[(2E,6E,10E,14E)-16-hydroxy-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenyl]-3-methylnaphthalene-1,4-dione
• CAS: 934831-09-1
• 化学式: C₃₁H₄₀O₃
• 分子量: 460.657
• InChiKey: RPXZMNAKSDAWRS-PUTDXGHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  omega-Hydroxymenaquinone-4 在 重铬酸吡啶 作用下， 以 二氯甲烷 为溶剂， 以51%的产率得到(2E,6E,10E,14E)-16-(1,4-dihydro-2-methyl-1,4-dioxonaphthalen-3-yl)-2,6,10,14-tetramethylhexadeca-2,6,10,14-tetraenal
  参考文献：
  名称：

  维生素K2的生物活性类似物的设计和合成：用培养的人类细胞系评估其生物活性。

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2007.12.025
• 作为产物：
  描述：

  2-((2E,6E,10E,14E)-16-(1,4-dimethoxy-2-methylnaphthalen-3-yl)-2,6,10,14-tetramethylhexadeca-2,6,10,14-tetraenyloxy)-tetrahydro-2H-pyran 在 ammonium cerium(IV) nitrate 作用下， 以 乙醚 、 水 、 乙腈 为溶剂， 以71%的产率得到omega-Hydroxymenaquinone-4
  参考文献：
  名称：

  维生素K2的生物活性类似物的设计和合成：用培养的人类细胞系评估其生物活性。

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2007.12.025

文献信息

• 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.
• Cytochrome P450-Dependent Catabolism of Vitamin K: ω-Hydroxylation Catalyzed by Human CYP4F2 and CYP4F11
  作者：Katheryne Z. Edson、Bhagwat Prasad、Jashvant D. Unadkat、Yoshitomo Suhara、Toshio Okano、F. Peter Guengerich、Allan E. Rettie

  DOI：10.1021/bi401208m

  日期：2013.11.19

  Vitamin K plays an essential role in many biological processes including blood clotting, maintenance of bone health, and inhibition of arterial calcification. A menaquinone form of vitamin K, MK4, is increasingly recognized for its key roles in mitochondria] electron transport, as a ligand for the nuclear receptor SXR, which controls the expression of genes involved in transport and metabolism of endo- and xenobiotics, and as a pharmacotherapeutic in the treatment of osteoporosis. Although cytochrome P450 (CYP) 4F2 activity is recognized as an important determinant of phylloquinone (K1) metabolism, the enzymes involved in menaquinone catabolism have not been studied previously. CYP4F2 and CYP4F11 were expressed and purified and found to be equally efficient as in vitro catalysts of MK4 whydroxylation. CYP4F2, but not CYP4F11, catalyzed sequential metabolism of MK4 to the wacid without apparent release of the intermediate aldehyde. The omega-alcohol could also be metabolized to the acid by microsomal NADtdependent alcohol and aldehyde dehydrogenases. LC MS/MS analysis of trypsinized human liver microsomes (using a surrogate peptide approach) revealed the mean concentrations of CYP4F2 and CYP4F11 to be 14.3 and 8.4 pmol/mg protein, respectively. Microsomal MK4 w-hydroxylation activities correlated with the CYP4F2 V433M genotype but not the CYP4F11 D446N genotype. Collectively, these data expand the lexicon of vitamin K w-hydroxylases to include the 'orphan' P450 CYP4F11 and identify a common variant, CYP4F2 (rs2108622), as a major pharmacogenetic variable influencing MK4 catabolism.
• 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。