3-fluoro-2-methoxy-6-(2-propenyl)-benzoic acid (1S,3R,4S)-3-(methoxymethoxy)-1-[2-[(4-methoxyphenyl)methoxy]ethyl]-4-methyl-6-heptenyl ester | 1107631-32-2

• 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: 3-fluoro-2-methoxy-6-(2-propenyl)-benzoic acid (1S,3R,4S)-3-(methoxymethoxy)-1-[2-[(4-methoxyphenyl)methoxy]ethyl]-4-methyl-6-heptenyl ester
• 英文别名: [(3S,5R,6S)-5-(methoxymethoxy)-1-[(4-methoxyphenyl)methoxy]-6-methylnon-8-en-3-yl] 3-fluoro-2-methoxy-6-prop-2-enylbenzoate
• CAS: 1107631-32-2
• 化学式: C₃₁H₄₁FO₇
• 分子量: 544.661
• InChiKey: LKHZWHMQUQVQFS-CVTPTMSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  39
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-fluoro-2-methoxy-6-(2-propenyl)-benzoic acid (1S,3R,4S)-3-(methoxymethoxy)-1-[2-[(4-methoxyphenyl)methoxy]ethyl]-4-methyl-6-heptenyl ester 在 Grubbs catalyst first generation 作用下， 以 二氯甲烷 为溶剂， 反应 0.78h， 生成 、 (3S,5R,6S,8E)-3,4,5,6,7,10-hexahydro-13-fluoro-14-methoxy-5-(methoxymethoxy)-3-[2-[(4-methoxyphenyl)methoxy]ethyl]-6-methyl-1H-2-benzoxacyclododecin-1-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide

  摘要：

  Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as F-19-NMR spectroscopy.

  DOI：

  10.1021/jm801265e
• 作为产物：
  描述：

  3-fluoro-2-methoxy-6-(2-propenyl)benzoic acid 、 (3R,5R,6S)-1-(4-methoxybenzyloxy)-5-(methoxymethoxy)-6-methylnon-8-en-3-ol 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 乙醚 、 甲苯 为溶剂， 以91%的产率得到3-fluoro-2-methoxy-6-(2-propenyl)-benzoic acid (1S,3R,4S)-3-(methoxymethoxy)-1-[2-[(4-methoxyphenyl)methoxy]ethyl]-4-methyl-6-heptenyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide

  摘要：

  Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as F-19-NMR spectroscopy.

  DOI：

  10.1021/jm801265e

文献信息

• Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide
  作者：Yoshinori Sugimoto、Keiichi Konoki、Michio Murata、Masafumi Matsushita、Hiroshi Kanazawa、Tohru Oishi

  DOI：10.1021/jm801265e

  日期：2009.2.12

  Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as F-19-NMR spectroscopy.