(2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl benzoate | 81189-93-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl benzoate
• 英文别名: (S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-benzoyloxy-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester；benzoyl lovastatin；[(2R,4R)-2-[2-[(1S,2S,6R,8S,8aR)-2,6-dimethyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]ethyl]-6-oxooxan-4-yl] benzoate
• CAS: 81189-93-7
• 化学式: C₃₁H₄₀O₆
• 分子量: 508.655
• InChiKey: DLKLOOVIXMMURY-GMOCJZLGSA-N

物化性质

• 沸点：
  638.3±55.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl benzoate 在 四氢吡咯 、 盐酸 、 正丁基锂 、 硫酸 、 原甲酸三乙酯 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 55.83h， 生成 辛伐他汀
  参考文献：
  名称：

  降胆固醇药辛伐他汀合成的新方法

  摘要：

  报道了一种从天然洛伐他汀制备降胆固醇药物辛伐他汀的新合成方法。该合成首先采用洛伐他汀（1）的OH基团的保护，然后采用内酯CO基团的保护以防止通过转化为原酸酯4a和4b来烯醇化。然后成功地实现了2-甲基丁酸酯侧链的烷基化。去除保护基得到抗高胆固醇血症药物辛伐他汀（2）。

  DOI：

  10.1002/hlca.200390066
• 作为产物：
  描述：

  苯甲酰氯 、 洛伐他汀 在 吡啶 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以91%的产率得到(2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl benzoate
  参考文献：
  名称：

  降胆固醇药辛伐他汀合成的新方法

  摘要：

  报道了一种从天然洛伐他汀制备降胆固醇药物辛伐他汀的新合成方法。该合成首先采用洛伐他汀（1）的OH基团的保护，然后采用内酯CO基团的保护以防止通过转化为原酸酯4a和4b来烯醇化。然后成功地实现了2-甲基丁酸酯侧链的烷基化。去除保护基得到抗高胆固醇血症药物辛伐他汀（2）。

  DOI：

  10.1002/hlca.200390066

文献信息

• WMJ-S-001, a novel aliphatic hydroxamate derivative, exhibits anti-inflammatory properties via MKP-1 in LPS-stimulated RAW264.7 macrophages
  作者：Wei-Chuan Chen、Chia-Sheng Yen、Wei-Jan Huang、Ya-Fen Hsu、George Ou、Ming-Jen Hsu

  DOI：10.1111/bph.13040

  日期：2015.4

  Background and PurposeHydroxamate derivatives have attracted considerable attention because of their broad pharmacological properties. Recent studies reported their potential use in the treatment of cardiovascular diseases, arthritis and infectious diseases. However, the mechanisms of the anti‐inflammatory effects of hydroxamate derivatives remain to be elucidated. In an effort to develop a novel pharmacological agent that could suppress abnormally activated macrophages, we investigated a novel aliphatic hydroxamate derivative, WMJ‐S‐001, and explored its anti‐inflammatory mechanisms.Experimental ApproachRAW264.7 macrophages were exposed to LPS in the absence or presence of WMJ‐S‐001. COX‐2 expression and signalling molecules activated by LPS were assessed.Key ResultsLPS‐induced COX‐2 expression was suppressed by WMJ‐S‐001. WMJ‐S‐001 inhibited p38MAPK, NF‐κB subunit p65 and CCAAT/enhancer‐binding protein (C/EBP)β phosphorylation in cells exposed to LPS. Treatment of cells with a p38MAPK inhibitor (p38MAPK inhibitor III) markedly inhibited LPS‐induced p65 and C/EBPβ phosphorylation and COX‐2 expression. LPS‐increased p65 and C/EBPβ binding to the COX‐2 promoter region was suppressed in the presence of WMJ‐S‐001. In addition, WMJ‐S‐001 suppression of p38MAPK, p65 and C/EBPβ phosphorylation, and subsequent COX‐2 expression were restored in cells transfected with a dominant‐negative (DN) mutant of MAPK phosphatase‐1 (MKP‐1). WMJ‐S‐001 also caused an increase in MKP‐1 activity in RAW264.7 macrophages.Conclusions and ImplicationsWMJ‐S‐001 may activate MKP‐1, which then dephosphorylates p38MAPK, resulting in a decrease in p65 and C/EBPβ binding to the COX‐2 promoter region and COX‐2 down‐regulation in LPS‐stimulated RAW264.7 macrophages. The present study suggests that WMJ‐S‐001 may be a potential drug candidate for alleviating LPS‐associated inflammatory diseases.
• Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species
  作者：Ruo-Kai Lin、Yuh-Feng Lin、Ming-Jen Hsu、Chang-Lin Hsieh、Chen-Yu Wang、Chih-Chiang Huang、Wei-Jan Huang

  DOI：10.1016/j.bmcl.2016.10.005

  日期：2016.11

  Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40 mu M had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation. (C) 2016 Elsevier Ltd. All rights reserved.
• A New Method for the Synthesis of Antihypercholesterolemic Agent Simvastatin
  作者：Kadir Dabak、Mustafa Adiyaman

  DOI：10.1002/hlca.200390066

  日期：2003.3

  A new synthetic method for the preparation of the cholesterol-lowering drug simvastatin from the naturally occurring lovastatin is reported. The synthesis employs first the protection of the OH group of lovastatin (1) and then the protection of the lactone CO group to prevent enolization via conversion to the orthoesters 4a and 4b. Alkylation of the 2-methylbutyrate side chain is then successfully

  报道了一种从天然洛伐他汀制备降胆固醇药物辛伐他汀的新合成方法。该合成首先采用洛伐他汀（1）的OH基团的保护，然后采用内酯CO基团的保护以防止通过转化为原酸酯4a和4b来烯醇化。然后成功地实现了2-甲基丁酸酯侧链的烷基化。去除保护基得到抗高胆固醇血症药物辛伐他汀（2）。