12α-[[(tert-butyl)dimethylsilyl]oxy]-4α-(2-propenyl)-5α-cholest-24-en-3-one | 250605-93-7

• 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: 12α-[[(tert-butyl)dimethylsilyl]oxy]-4α-(2-propenyl)-5α-cholest-24-en-3-one
• CAS: 250605-93-7
• 化学式: C₃₆H₆₂O₂Si
• 分子量: 554.973
• InChiKey: STKTUPNLEJCHAZ-PTVUWHSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  39.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  12α-[[(tert-butyl)dimethylsilyl]oxy]-4α-(2-propenyl)-5α-cholest-24-en-3-one 在 四丁基氟化铵 、 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 反应 50.0h， 生成 12α-hydroxy-4α-(2-propenyl)-5α-cholest-24-en-3α-ol
  参考文献：
  名称：

  Synthesis and in vitro biological activity of 4α-(2-propenyl)-5α-cholest-24-en-3α,12α-diol, a 12α-hydroxyl analog of 4α-(2-propenyl)-5α-cholest-24-en-3α-ol: The latter is a potent activator of the low-density lipoprotein receptor promoter

  摘要：

  4 alpha-(2-Propenyl)-5 alpha-cholest-24-en-3 alpha-ol (3) was shown recently in a Chinese hamster ovary (CHO) cell-based low-density lipoprotein receptor/luciferase (LDLR/Luc) assay to be a potent transcriptional activator of the LDL receptor promoter in the presence of 25-hydroxycholesterol. Because of the involvement of 12 alpha-hydroxylation in the metabolism of cholesterol, we are interested in investigating the effect of introducing a 12 alpha-hydroxyl group to 3 on the transcriptional activity of the LDL receptor promoter. Thus 4 alpha-(2-propenyl)-5 alpha-cholest-24-en-3 alpha,12 alpha-diol (14), a 12 alpha-hydroxyl analog of 3, was synthesized from deoxycholic acid via the formation of 12 alpha-[[(tert-butyl)dimethylsilyl]oxy]-4 alpha-(2-propenyl (11). Test results show that 14 is inactive at concentrations of up to 20 mu g/ml, compared to 3 with an EC30 value of 2.6 mu M, in the CHO cell-based LDLR/Lac assay. Apparently introduction of a 12 alpha-hydroxyl group abolishes the capability of 3 alpha-sterol 14 to activate the transcription of the LDL receptor promoter. However, in the [1-(14)Cacetate]cholesterol biosynthesis inhibition assay in CHO cells, 14 at 10 mu g/ml (23 mu M) is shown to inhibit the cholesterol biosynthesis by 51% relative to the control cells. Our previous studies indicated that 3 showed a 38% inhibition, but 4 alpha-(2-propenyl)-5 alpha-cholestan-3 alpha-ol (1) exhibited no inhibition in the same assay at 10 mu g/ml. In summary the results indicate that, in addition to the 24,25-unsaturation, the 12 alpha-hydroxyl group in 14 has also conferred an inhibitory effect on cholesterol biosynthesis in CHO cells; however, the inhibition of cholesterol biosynthesis by 14 does not lead to the transcriptional activation of the LDL receptor promoter. (C) 1999 Published by Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00053-7
• 作为产物：
  描述：

  N-methyl-N-(methyloxy)-3,3-(ethylenedioxy)-12α-hydroxychol-5-en-24-amide 在 2,6-二甲基吡啶 、 盐酸 、 lithium aluminium tetrahydride 、 氨 、 lithium 、 叔丁醇 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 55.17h， 生成 12α-[[(tert-butyl)dimethylsilyl]oxy]-4α-(2-propenyl)-5α-cholest-24-en-3-one
  参考文献：
  名称：

  Synthesis and in vitro biological activity of 4α-(2-propenyl)-5α-cholest-24-en-3α,12α-diol, a 12α-hydroxyl analog of 4α-(2-propenyl)-5α-cholest-24-en-3α-ol: The latter is a potent activator of the low-density lipoprotein receptor promoter

  摘要：

  4 alpha-(2-Propenyl)-5 alpha-cholest-24-en-3 alpha-ol (3) was shown recently in a Chinese hamster ovary (CHO) cell-based low-density lipoprotein receptor/luciferase (LDLR/Luc) assay to be a potent transcriptional activator of the LDL receptor promoter in the presence of 25-hydroxycholesterol. Because of the involvement of 12 alpha-hydroxylation in the metabolism of cholesterol, we are interested in investigating the effect of introducing a 12 alpha-hydroxyl group to 3 on the transcriptional activity of the LDL receptor promoter. Thus 4 alpha-(2-propenyl)-5 alpha-cholest-24-en-3 alpha,12 alpha-diol (14), a 12 alpha-hydroxyl analog of 3, was synthesized from deoxycholic acid via the formation of 12 alpha-[[(tert-butyl)dimethylsilyl]oxy]-4 alpha-(2-propenyl (11). Test results show that 14 is inactive at concentrations of up to 20 mu g/ml, compared to 3 with an EC30 value of 2.6 mu M, in the CHO cell-based LDLR/Lac assay. Apparently introduction of a 12 alpha-hydroxyl group abolishes the capability of 3 alpha-sterol 14 to activate the transcription of the LDL receptor promoter. However, in the [1-(14)Cacetate]cholesterol biosynthesis inhibition assay in CHO cells, 14 at 10 mu g/ml (23 mu M) is shown to inhibit the cholesterol biosynthesis by 51% relative to the control cells. Our previous studies indicated that 3 showed a 38% inhibition, but 4 alpha-(2-propenyl)-5 alpha-cholestan-3 alpha-ol (1) exhibited no inhibition in the same assay at 10 mu g/ml. In summary the results indicate that, in addition to the 24,25-unsaturation, the 12 alpha-hydroxyl group in 14 has also conferred an inhibitory effect on cholesterol biosynthesis in CHO cells; however, the inhibition of cholesterol biosynthesis by 14 does not lead to the transcriptional activation of the LDL receptor promoter. (C) 1999 Published by Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00053-7