4-fluoromethyl-1,6-heptadien-4-ol | 2267-53-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-fluoromethyl-1,6-heptadien-4-ol
• 英文别名: 4-fluoromethyl-hepta-1,6-dien-4-ol；4-Fluormethylhepta-1,6-dien-4-ol；Fluormethyl-diallyl-carbinol；4-(Fluoromethyl)hepta-1,6-dien-4-ol
• CAS: 2267-53-0
• 化学式: C₈H₁₃FO
• 分子量: 144.189
• InChiKey: LJBVFTKRZZKBPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  10
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-fluoromethyl-1,6-heptadien-4-ol 在 臭氧 、 硫酸 、 双氧水 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.5h， 生成 3-Hydroxy-3-fluormethyl-glutarsaeure
  参考文献：
  名称：

  Synthesis of mevalonate- and fluorinated mevalonate prodrugs and their in vitro human plasma stability

  摘要：

  The mevalonate pathway is essential for the production of many important molecules in lipid biosynthesis. Inhibition of this pathway is the mechanism of statin cholesterol-lowering drugs, as well as the target of drugs to treat osteoporosis, to combat parasites, and to inhibit tumor cell growth. Unlike the human mevalonate pathway, the bacterial pathway appears to be regulated by diphosphomevalonate (DPM). Enzymes in the mevalonate pathway act to produce isopentenyl diphosphate, the product of the DPM decarboxylase reaction, utilize phosphorylated (charged) intermediates, which are poorly bioavailable. It has been shown that fluorinated DPMs (6-fluoro- and 6,6,6-trifluoro-5diphosphomevalonate) are excellent inhibitors of the bacterial pathway; however, highly charged DPM and analogs are not bioavailable. To increase cellular permeability of mevalonate analogs, we have synthesized various prodrugs of mevalonate and 6-fluoro- and 6,6,6-trifluoromevalonate that can be enzymatically transformed to the corresponding DPM or fluorinated DPM analogs by esterases or amidases. To probe the required stabilities as potentially bioavailable prodrugs, we measured the half-lives of esters, amides, carbonates, acetals, and ketal promoieties of mevalonate and the fluorinated mevalonate analogs in human blood plasma. Stability studies showed that the prodrugs are converted to the mevalonates in human plasma with a wide range of half-lives. These studies provide stability data for a variety of prodrug options having varying stabilities and should be very useful in the design of appropriate prodrugs of mevalonate and fluorinated mevalonates. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.040
• 作为产物：
  描述：

  氟乙酸乙酯 、 烯丙基溴化镁 以 乙醚 为溶剂， 反应 0.33h， 生成 4-fluoromethyl-1,6-heptadien-4-ol
  参考文献：
  名称：

  [EN] PRODRUGS OF FLUORINATED MEVALONATES TO INHIBIT THE MEVALONATE PATHWAY OF STREPTOCOCCUS PNEUMONIAE
  [FR] PROMÉDICAMENTS DE MÉVALONATES FLUORÉS POUR INHIBER LA VOIE DU MÉVALONATE DU PNEUMOCOQUE

  摘要：

  公开号：

  WO2013130792A3

文献信息

• Tschesche,R.; Machleidt,H., Justus Liebigs Annalen der Chemie, 1960, vol. 631, p. 61 - 76
  作者：Tschesche,R.、Machleidt,H.

  DOI：——

  日期：——
• 671. Organic fluorine compounds. Part XXII. Fluorine analogues of mevalonic acid
  作者：Ernst D. Bergmann、Sasson Cohen

  DOI：10.1039/jr9610003457

  日期：——
• Shuto, Akira; Kuwano, Eiichi; Eto, Morifusa, Agricultural and Biological Chemistry, 1988, vol. 52, # 4, p. 915 - 920
  作者：Shuto, Akira、Kuwano, Eiichi、Eto, Morifusa

  DOI：——

  日期：——
• SHUTO, AKIRA;KUWANO, EIICHI;ETO, MORIFUSA, AGR. AND BIOL. CHEM., 52,(1988) N 4, 915-919
  作者：SHUTO, AKIRA、KUWANO, EIICHI、ETO, MORIFUSA

  DOI：——

  日期：——
• Prodrugs of Fluorinated Mevalonates to Inhibit the Mevalonate Pathway of Streptococcus pneumoniae
  申请人：Silverman Richard B.

  公开号：US20130245284A1

  公开（公告）日：2013-09-19

  Fluorinated prodrug compounds as can be used for selective streptococcal mevalonate pathway inhibition.