(8R)-8-(hydroxymethyl)-9-oxa-1,5-dithiaspiro[5.5]undecan-10-ol | 135304-61-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫代缩醛
• 英文名称: (8R)-8-(hydroxymethyl)-9-oxa-1,5-dithiaspiro[5.5]undecan-10-ol
• CAS: 135304-61-9；135413-40-0
• 化学式: C₉H₁₆O₃S₂
• 分子量: 236.356
• InChiKey: FZOWQPYAFMVHIL-GVHYBUMESA-N

物化性质

• 沸点：
  447.6±45.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (8R)-8-(hydroxymethyl)-9-oxa-1,5-dithiaspiro[5.5]undecan-10-ol 在 吡啶 、 高氯酸亚汞 、 溴脲苷 、 calcium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 62.0h， 生成 6,8-二氧杂二环[3.2.1]辛烷-3-酮,(1R)-
  参考文献：
  名称：

  Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability

  摘要：

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

  DOI：

  10.1021/jm960301c
• 作为产物：
  描述：

  2-(2,2-dimethoxyethyl)1,3-dithiane 在 盐酸 、 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 22.5h， 生成 (8R)-8-(hydroxymethyl)-9-oxa-1,5-dithiaspiro[5.5]undecan-10-ol
  参考文献：
  名称：

  Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability

  摘要：

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

  DOI：

  10.1021/jm960301c

文献信息

• Bryostatins: The asymmetric synthesis of C1-C9 and C11-C16 fragments
  作者：J. De Brabander、K. Vanhessche、M. Vandewalle

  DOI：10.1016/0040-4039(91)85096-n

  日期：1991.6

  The fragments C1-C-9 19 and C-11-C-16 26 of the bryostatins are constructed in an enantioselective and highly diastereoselective fashion from respectively D-pantolactone (2) and L-erythrulose (3) as chiral templates.
• Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability
  作者：Daniel Delorme、Yves Ducharme、Christine Brideau、Chi-Chung Chan、Nathalie Chauret、Sylvie Desmarais、Daniel Dubé,、Jean-Pierre Falgueyret、Réjean Fortin、Jocelyne Guay、Pierre Hamel、Tom R. Jones、Carole Lépine、Chun Li、Malia McAuliffe、Cyril S. McFarlane、Deborah A. Nicoll-Griffith、Denis Riendeau、James A. Yergey、Yves Girard

  DOI：10.1021/jm960301c

  日期：1996.1.1

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).