(2R,3S)-α²-(1-hydroxyethyl)-1,4-dioxaspiro[4,5]decane-2,3-dimethanol | 524714-08-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3S)-α²-(1-hydroxyethyl)-1,4-dioxaspiro[4,5]decane-2,3-dimethanol
• 英文别名: (1S,2S)-1-[(2S,3R)-2-(hydroxymethyl)-1,4-dioxaspiro[4.5]decan-3-yl]propane-1,2-diol
• CAS: 524714-08-7
• 化学式: C₁₂H₂₂O₅
• 分子量: 246.304
• InChiKey: HYILHWVCLWZRHL-NAKRPEOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S)-α²-(1-hydroxyethyl)-1,4-dioxaspiro[4,5]decane-2,3-dimethanol 在 sodium hydroxide 、 sodium periodate 、 正丁基锂 、 四正丁基硫酸铵 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 、 甲苯 为溶剂， 反应 21.0h， 生成 1,1-dimethylethyl [[(2S,3R)-3-[(1E,3Z)-6-(trimethylsilyl)-1,3-hexadien-5-ynyl]-1,4-dioxaspiro[4,5]dec-2-yl]methoxy]ethanoate
  参考文献：
  名称：

  Novel 3-Oxa Lipoxin A₄ Analogues with Enhanced Chemical and Metabolic Stability Have Anti-inflammatory Activity in Vivo

  摘要：

  Lipoxin A(4) (LXA(4)) is a structurally and functionally distinct natural product called an eicosanoid, which displays immunomodulatory and anti-inflammatory activity but is rapidly metabolized to inactive catabolites in vivo. A previously described analogue of LXA(4), methyl (5R,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-7,9,11,13-hexadecatetraenoate (2, ATLa), was shown to have a poor pharmacokinetic profile after both oral and intravenous administration, as well as sensitivity to acid and light. The chemical stability of the corresponding E,E,E-trien-11-yne analogue, 3, was improved over 2 without loss of efficacy in the mouse air pouch model of inflammation. Careful analysis of the plasma samples from the pharmacokinetic assays for both 2 and 3 identified a previously undetected metabolite, which is consistent with metabolism by beta-oxidation. The formation of the oxidative metabolites was eliminated with the corresponding 3-oxatetraene, 4, and the 3-oxatrien-11-yne, 5, analogues of 2. Evaluation of 3-oxa analogues 4 and 5 in calcium ionophore-induced acute skin inflammation model demonstrated similar topical potency and efficacy compared to 2. The 3-oxatrien-11-yne analogue, 5, is equipotent to 2 in an animal model of inflammation but has enhanced metabolic and chemical stability and a greatly improved pharmacokinetic profile.

  DOI：

  10.1021/jm030569l
• 作为产物：
  描述：

  (2R,3R)-3-(1,2-dihydroxypropyl)-1,4-dioxaspiro[4,5]decane-2-carboxaldehyde 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以88%的产率得到(2R,3S)-α²-(1-hydroxyethyl)-1,4-dioxaspiro[4,5]decane-2,3-dimethanol
  参考文献：
  名称：

  Novel 3-Oxa Lipoxin A₄ Analogues with Enhanced Chemical and Metabolic Stability Have Anti-inflammatory Activity in Vivo

  摘要：

  Lipoxin A(4) (LXA(4)) is a structurally and functionally distinct natural product called an eicosanoid, which displays immunomodulatory and anti-inflammatory activity but is rapidly metabolized to inactive catabolites in vivo. A previously described analogue of LXA(4), methyl (5R,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-7,9,11,13-hexadecatetraenoate (2, ATLa), was shown to have a poor pharmacokinetic profile after both oral and intravenous administration, as well as sensitivity to acid and light. The chemical stability of the corresponding E,E,E-trien-11-yne analogue, 3, was improved over 2 without loss of efficacy in the mouse air pouch model of inflammation. Careful analysis of the plasma samples from the pharmacokinetic assays for both 2 and 3 identified a previously undetected metabolite, which is consistent with metabolism by beta-oxidation. The formation of the oxidative metabolites was eliminated with the corresponding 3-oxatetraene, 4, and the 3-oxatrien-11-yne, 5, analogues of 2. Evaluation of 3-oxa analogues 4 and 5 in calcium ionophore-induced acute skin inflammation model demonstrated similar topical potency and efficacy compared to 2. The 3-oxatrien-11-yne analogue, 5, is equipotent to 2 in an animal model of inflammation but has enhanced metabolic and chemical stability and a greatly improved pharmacokinetic profile.

  DOI：

  10.1021/jm030569l