D-1,2-di-O-butyl-myo-inositol | 205247-22-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: D-1,2-di-O-butyl-myo-inositol
• 英文别名: D-2,3-Di-O-butyl-myo-inositol；(1R,2S,3S,4R,5S,6R)-5,6-dibutoxycyclohexane-1,2,3,4-tetrol
• CAS: 205247-22-9
• 化学式: C₁₄H₂₈O₆
• 分子量: 292.373
• InChiKey: OUSKZQZPFFHJFL-DHRKEOQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  99.4
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  D-1,2-di-O-butyl-myo-inositol 在 palladium on activated charcoal 四氮唑 、 氢气 、 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 D-1,2-di-O-butyl-myo-inositol 3,4,5,6-tetrakis(dihydrogen phosphate)
  参考文献：
  名称：

  Antagonists of myo-inositol 3,4,5,6-tetrakisphosphate allow repeated epithelial chloride secretion

  摘要：

  Cystic fibrosis (CF) patients suffer from a defect in hydration of mucosal membranes due to mutations in the cystic fibrosis transmembrane regulator (CFTR), an apical chloride channel in mucosal epithelia. Disease expression in CF knockout mice is organ specific, varying with the level of expression of calcium activated Cl- channels (CLCA). Therefore, restoring transepithelial Cl- secretion by augmenting alternate Cl- channels, such as CLCA, could be beneficial. However, CLCA-mediated Cl- secretion is transient, due in part to the inhibitory effects of myo-inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P-4]. This suggests that antagonists of Ins(3,4,5,6)P-4 could be useful in treatment of CF. We have, therefore, synthesized a series of membrane-permeant Ins(3,4,5,6)P-4 derivatives, carrying alkyl substituents on the hydroxyl groups and screened them for effects on Cl- secretion in a human colonic epithelial cell line, T-84, While membrane-permeant Ins(3,4,5,6)P-4 derivatives had no direct effects on carbachol-stimulated Cl- secretion, Ins(3,4,5,6)P-4 derivatives, but not enantiomeric Ins(1,4,5,6)P-4 derivatives, reversed the inhibitory effect of Ins(3,4,5,6)P-4 on subsequent thapsigargin activation of Cl- secretion. The extent of the antagonistic effect of the Ins(3,4,5,6)P-4 derivatives varied with the position of the alkyl substituents. Derivatives with a cyclohexylidene ketal or a butyl-chain at the 1-position reversed the Ins(3,4,5,6)P-4-mediated inhibition of Cl- secretion by up to 96 and 85%, respectively, whereas butylation of the 1- and 2-position generated a reversal effect of only 65%. Derivatives carrying the butyl chain only at the 2-position showed no antagonistic effect. These data: (1) Support the hypothesis that Ins(3,4,5,6)P-4 stereospecifically inhibits Ca2+ activated Cl- secretion and that Ins(3,4,5,6)P-4 mediates most, if not all of the cholinergic-mediated inhibition of chloride secretion in T84 cells; (2) Demonstrate Ins(3,4,5,6)P-4-mediated inhibition can be completely reversed with rationally designed membrane-permeant Ins(3,4,5,6)P4 antagonists; (3) Demonstrate that a SAR for membrane-permeant Ins(3,4,5,6) P-4 antagonists can be generated and screened in a physiologically relevant cell-based assay; (4) Indicate that Ins(3,4,5,6)P-4 derivatives could serve as a starting point for the development of therapeutics to treat cystic fibrosis. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00188-3
• 作为产物：
  描述：

  D-3,4,5,6-tetra-O-benzyl-1,2-di-O-butyl-myo-inositol 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以92%的产率得到D-1,2-di-O-butyl-myo-inositol
  参考文献：
  名称：

  Antagonists of myo-inositol 3,4,5,6-tetrakisphosphate allow repeated epithelial chloride secretion

  摘要：

  Cystic fibrosis (CF) patients suffer from a defect in hydration of mucosal membranes due to mutations in the cystic fibrosis transmembrane regulator (CFTR), an apical chloride channel in mucosal epithelia. Disease expression in CF knockout mice is organ specific, varying with the level of expression of calcium activated Cl- channels (CLCA). Therefore, restoring transepithelial Cl- secretion by augmenting alternate Cl- channels, such as CLCA, could be beneficial. However, CLCA-mediated Cl- secretion is transient, due in part to the inhibitory effects of myo-inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P-4]. This suggests that antagonists of Ins(3,4,5,6)P-4 could be useful in treatment of CF. We have, therefore, synthesized a series of membrane-permeant Ins(3,4,5,6)P-4 derivatives, carrying alkyl substituents on the hydroxyl groups and screened them for effects on Cl- secretion in a human colonic epithelial cell line, T-84, While membrane-permeant Ins(3,4,5,6)P-4 derivatives had no direct effects on carbachol-stimulated Cl- secretion, Ins(3,4,5,6)P-4 derivatives, but not enantiomeric Ins(1,4,5,6)P-4 derivatives, reversed the inhibitory effect of Ins(3,4,5,6)P-4 on subsequent thapsigargin activation of Cl- secretion. The extent of the antagonistic effect of the Ins(3,4,5,6)P-4 derivatives varied with the position of the alkyl substituents. Derivatives with a cyclohexylidene ketal or a butyl-chain at the 1-position reversed the Ins(3,4,5,6)P-4-mediated inhibition of Cl- secretion by up to 96 and 85%, respectively, whereas butylation of the 1- and 2-position generated a reversal effect of only 65%. Derivatives carrying the butyl chain only at the 2-position showed no antagonistic effect. These data: (1) Support the hypothesis that Ins(3,4,5,6)P-4 stereospecifically inhibits Ca2+ activated Cl- secretion and that Ins(3,4,5,6)P-4 mediates most, if not all of the cholinergic-mediated inhibition of chloride secretion in T84 cells; (2) Demonstrate Ins(3,4,5,6)P-4-mediated inhibition can be completely reversed with rationally designed membrane-permeant Ins(3,4,5,6)P4 antagonists; (3) Demonstrate that a SAR for membrane-permeant Ins(3,4,5,6) P-4 antagonists can be generated and screened in a physiologically relevant cell-based assay; (4) Indicate that Ins(3,4,5,6)P-4 derivatives could serve as a starting point for the development of therapeutics to treat cystic fibrosis. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00188-3