1-[(3S,5S,8S,9R,10R,13R,14R,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl]-ethanone | 210692-31-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 1-[(3S,5S,8S,9R,10R,13R,14R,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl]-ethanone
• 英文别名: 1-[(3S,5S,8S,9R,10R,13R,14R,17R)-3-[tert-butyl(dimethyl)silyl]oxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
• CAS: 210692-31-2
• 化学式: C₂₇H₄₈O₂Si
• 分子量: 432.762
• InChiKey: KVIJXOCKOIHXGP-VPAXRLSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.62
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[(3S,5S,8S,9R,10R,13R,14R,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl]-ethanone 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以97%的产率得到(3β,5α,8α,9β,10α,13α,14β,17α)-3-hydroxypregnan-20-one
  参考文献：
  名称：

  Neurosteroid Analogues. 6. The Synthesis and GABA_A Receptor Pharmacology of Enantiomers of Dehydroepiandrosterone Sulfate, Pregnenolone Sulfate, and (3α,5β)-3-Hydroxypregnan-20-one Sulfate

  摘要：

  The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone sulfate (2), and (3 alpha,5 beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4-6, respectively, were prepared by total steroid synthesis. The enantioselectivity of the compounds as negative modulators of the GABA(A) receptors present in cultured rat hippocampal neurons was examined using electrophysiological methods. Enantioselectivity was found for the inhibitory actions of the dehydroepiandrosterone enantiomers, The IC(50)s for compounds 1 and 4 were 11 +/- 1 and 80 +/- 14 mu M, respectively. Little, if any, enantioselectivity was found for the other two pairs of steroid sulfate inhibitors. The IC(50)s for compounds 2 and 5 were 82 +/- 12 and 76 +/- 27 mu M, respectively. The IC(50)s for compounds 3 and 6 were 39 +/- 7 and 46 +/- 2 mu M, respectively. The results suggest that the sites of action for the androstane and pregnane series of steroid sulfate blockers of GABA-mediated current are different. The observed enantioselectivity for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory actions are mediated via a chiral recognition site and provides new evidence in support of the earlier hypothesis that there is a binding site for this compound on GABA(A) receptors. Conversely, the failure to observe enantioselectivity for the actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral recognition site far these steroids does not exist on GABA(A) receptors and suggests that the effects of these compounds on this receptor's function may arise indirectly as a consequence of steroid-induced membrane perturbation.

  DOI：

  10.1021/jm980148h
• 作为产物：
  描述：

  dl-Δ⁴-androstene-3,17-dione 在 4-二甲氨基吡啶 、 sodium hydroxide 、 硼烷四氢呋喃络合物 、 dimsylsodium 、 potassium tert-butylate 、 双氧水 、 sodium acetate 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 47.0h， 生成 1-[(3S,5S,8S,9R,10R,13R,14R,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl]-ethanone
  参考文献：
  名称：

  Neurosteroid Analogues. 6. The Synthesis and GABA_A Receptor Pharmacology of Enantiomers of Dehydroepiandrosterone Sulfate, Pregnenolone Sulfate, and (3α,5β)-3-Hydroxypregnan-20-one Sulfate

  摘要：

  The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone sulfate (2), and (3 alpha,5 beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4-6, respectively, were prepared by total steroid synthesis. The enantioselectivity of the compounds as negative modulators of the GABA(A) receptors present in cultured rat hippocampal neurons was examined using electrophysiological methods. Enantioselectivity was found for the inhibitory actions of the dehydroepiandrosterone enantiomers, The IC(50)s for compounds 1 and 4 were 11 +/- 1 and 80 +/- 14 mu M, respectively. Little, if any, enantioselectivity was found for the other two pairs of steroid sulfate inhibitors. The IC(50)s for compounds 2 and 5 were 82 +/- 12 and 76 +/- 27 mu M, respectively. The IC(50)s for compounds 3 and 6 were 39 +/- 7 and 46 +/- 2 mu M, respectively. The results suggest that the sites of action for the androstane and pregnane series of steroid sulfate blockers of GABA-mediated current are different. The observed enantioselectivity for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory actions are mediated via a chiral recognition site and provides new evidence in support of the earlier hypothesis that there is a binding site for this compound on GABA(A) receptors. Conversely, the failure to observe enantioselectivity for the actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral recognition site far these steroids does not exist on GABA(A) receptors and suggests that the effects of these compounds on this receptor's function may arise indirectly as a consequence of steroid-induced membrane perturbation.

  DOI：

  10.1021/jm980148h

文献信息

• Neurosteroid Analogues. 6. The Synthesis and GABA_A Receptor Pharmacology of Enantiomers of Dehydroepiandrosterone Sulfate, Pregnenolone Sulfate, and (3α,5β)-3-Hydroxypregnan-20-one Sulfate
  作者：Kent R. Nilsson、Charles F. Zorumski、Douglas F. Covey

  DOI：10.1021/jm980148h

  日期：1998.7.1

  The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone sulfate (2), and (3 alpha,5 beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4-6, respectively, were prepared by total steroid synthesis. The enantioselectivity of the compounds as negative modulators of the GABA(A) receptors present in cultured rat hippocampal neurons was examined using electrophysiological methods. Enantioselectivity was found for the inhibitory actions of the dehydroepiandrosterone enantiomers, The IC(50)s for compounds 1 and 4 were 11 +/- 1 and 80 +/- 14 mu M, respectively. Little, if any, enantioselectivity was found for the other two pairs of steroid sulfate inhibitors. The IC(50)s for compounds 2 and 5 were 82 +/- 12 and 76 +/- 27 mu M, respectively. The IC(50)s for compounds 3 and 6 were 39 +/- 7 and 46 +/- 2 mu M, respectively. The results suggest that the sites of action for the androstane and pregnane series of steroid sulfate blockers of GABA-mediated current are different. The observed enantioselectivity for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory actions are mediated via a chiral recognition site and provides new evidence in support of the earlier hypothesis that there is a binding site for this compound on GABA(A) receptors. Conversely, the failure to observe enantioselectivity for the actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral recognition site far these steroids does not exist on GABA(A) receptors and suggests that the effects of these compounds on this receptor's function may arise indirectly as a consequence of steroid-induced membrane perturbation.