6-(t-butyldimethylsilyloxy)-1,3,5(10),6-estratetraene-3,17β-diol acetate | 518069-19-7

• 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: 6-(t-butyldimethylsilyloxy)-1,3,5(10),6-estratetraene-3,17β-diol acetate
• CAS: 518069-19-7
• 化学式: C₂₈H₄₀O₅Si
• 分子量: 484.708
• InChiKey: UBHKZXYBOURKRM-CTLMZRPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.83
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  6-(t-butyldimethylsilyloxy)-1,3,5(10),6-estratetraene-3,17β-diol acetate 在 吡啶 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 60.8h， 生成 7-perfluorohexyl-1,3,5(10),6-estratetraene-3,17β-diol diacetate
  参考文献：
  名称：

  Synthesis, Characterization and Biological Evaluation of 7α-Perfluoroalkylestradiol Derivatives

  摘要：

  Linkage of a long CH2 side chain ('spacer') onto C-7alpha of estradiol-17beta (E-2) does not abrogate the binding affinity of this hormone for its receptor. Our purpose was to assess whether the linkage of a CF2, side chain, which is more bulky and rigid, could also be accommodated by the estrogen receptor (ER). We describe here the synthesis of 7alpha-perfluorohexylestradiol 7 by perfluoroalkylation of a key silylenolether 2 with FITS-6 (perfluorohexyl-phenyliodonium trifluoromethanesulfonate). 7alpha-Trifluoromethylestradiol 10a was prepared as a fluorinated control compound by UV-light induced trifluoromethylation of 2 with Umemoto reagent (S-trifluoromethyldibenzo[b,d]thiophenium trifluoromethanesulfonate). Endocrine properties of these two E2 derivatives were tested on the MCF-7 breast cancer cell line. Our data reveal that rigidity of the side chain of 7 affected the association of its hormone moiety with the ER to the same extent as a long alkyl side chain. Rigidity also failed to abrogate estrogenicity, as demonstrated by the ability of 7 to enhance ERE-dependent transcription and cell growth. Compound 7 retained the capacity of inducing down regulation of the receptor. Interestingly, no evidence of antiestrogervicity was recorded since this compound behaved like a weak estrogen, exerting a mitogenic effect at high concentration. Of note, control 10a displayed a higher binding affinity than 7 for ER and consequently acted like the latter, albeit with a higher efficiency. Selection of appropriate residues to be linked at the end of a long 7alpha alkyl side chain is known to be essential for generating strong antiestrogervicity. One may hope that such a property may also hold for perfluorinated chains to produce antiestrogens with strong metabolic stability. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00457-1
• 作为产物：
  描述：

  叔丁基二甲硅基三氟甲磺酸酯 、 [(8R,9S,13S,14S,17S)-3-乙酰氧基-13-甲基-6-氧代-8,9,11,12,14,15,16,17-八氢-7H-环戊二烯并[a]菲-17-基]乙酸酯 在 2,6-二甲基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 90.0h， 以92%的产率得到6-(t-butyldimethylsilyloxy)-1,3,5(10),6-estratetraene-3,17β-diol acetate
  参考文献：
  名称：

  Synthesis, Characterization and Biological Evaluation of 7α-Perfluoroalkylestradiol Derivatives

  摘要：

  Linkage of a long CH2 side chain ('spacer') onto C-7alpha of estradiol-17beta (E-2) does not abrogate the binding affinity of this hormone for its receptor. Our purpose was to assess whether the linkage of a CF2, side chain, which is more bulky and rigid, could also be accommodated by the estrogen receptor (ER). We describe here the synthesis of 7alpha-perfluorohexylestradiol 7 by perfluoroalkylation of a key silylenolether 2 with FITS-6 (perfluorohexyl-phenyliodonium trifluoromethanesulfonate). 7alpha-Trifluoromethylestradiol 10a was prepared as a fluorinated control compound by UV-light induced trifluoromethylation of 2 with Umemoto reagent (S-trifluoromethyldibenzo[b,d]thiophenium trifluoromethanesulfonate). Endocrine properties of these two E2 derivatives were tested on the MCF-7 breast cancer cell line. Our data reveal that rigidity of the side chain of 7 affected the association of its hormone moiety with the ER to the same extent as a long alkyl side chain. Rigidity also failed to abrogate estrogenicity, as demonstrated by the ability of 7 to enhance ERE-dependent transcription and cell growth. Compound 7 retained the capacity of inducing down regulation of the receptor. Interestingly, no evidence of antiestrogervicity was recorded since this compound behaved like a weak estrogen, exerting a mitogenic effect at high concentration. Of note, control 10a displayed a higher binding affinity than 7 for ER and consequently acted like the latter, albeit with a higher efficiency. Selection of appropriate residues to be linked at the end of a long 7alpha alkyl side chain is known to be essential for generating strong antiestrogervicity. One may hope that such a property may also hold for perfluorinated chains to produce antiestrogens with strong metabolic stability. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00457-1