17β-<(tert-butyldimethylsilyl)oxy>androsta-4,6-dien-3-one | 115814-79-4

• 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: 17β-<(tert-butyldimethylsilyl)oxy>androsta-4,6-dien-3-one
• 英文别名: 17β-(t-butyldimethylsilyloxy)-androsta-4,6-dien-3-one；(8R,9S,10R,13S,14S,17S)-17-[tert-butyl(dimethyl)silyl]oxy-10,13-dimethyl-1,2,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one
• CAS: 115814-79-4
• 化学式: C₂₅H₄₀O₂Si
• 分子量: 400.677
• InChiKey: VPDLTJWFFOZUAH-BKWLFHPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.68
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  17β-<(tert-butyldimethylsilyl)oxy>androsta-4,6-dien-3-one 在 四氯化钛 oxonium 作用下， 以 二氯甲烷 为溶剂， 生成 17β-hydroxy-7α-allyl-4-androsten-3-one
  参考文献：
  名称：

  立体定向合成von7α-烯丙基和7α-丙基甾体

  摘要：

  DOI：

  10.1016/s0040-4039(00)80344-5
• 作为产物：
  描述：

  (17b)-17-羟基-雄甾-4,6-二烯-3-酮 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以94%的产率得到17β-<(tert-butyldimethylsilyl)oxy>androsta-4,6-dien-3-one
  参考文献：
  名称：

  通过共轭添加甲硅烷基铜酸酯试剂合成羟基化甾体激素。

  摘要：

  研究了通过将Fleming的甲硅烷基-杯酸酯试剂（PhMe2Si）2CuLi，一种被掩蔽的羟基缀合到适当的烯酮中来合成几种羟基化的类固醇。通过这种方法，从17个β-羟基雄甾烯-4,6-dien-3-one（1a）以良好的收率获得了7个α-羟基睾丸激素（7），尽管对17个β-羟基雄甾烯-1,4-dien-3的反应相似-一（8）产生低产率的1α-羟基睾丸酮（13）的主要原因是苯基甲硅烷基中间体向卤代硅烷的转化率低。以类似的方式从3 beta-hydroxy-5 alpha-pregn-16-en-20-one和5 alpha-cholestane-1获得3 beta，16 alpha-Dihydroxy-5 alpha-pregnan-20-one（18b）。通过共轭加成甲硅烷基，还原羰基官能团，由1-en-3-one（14）生成alpha，3 alpha-diol（17），

  DOI：

  10.1016/0039-128x(94)90102-3

文献信息

• Synthesis, Structure Elucidation, and Biochemical Evaluation of 7.alpha.- and 7.beta.-Arylaliphatic-Substituted Androst-4-ene-3,17-diones as Inhibitors of Aromatase
  作者：Jill M. O'Reilly、Naiyin Li、William L. Duax、Robert W. Brueggemeier

  DOI：10.1021/jm00015a006

  日期：1995.7

  The inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the conversion of androgens to estrogens, may be useful for the endocrine treatment of breast cancer. Previously, several 7 alpha-thio-substituted androstenediones have been shown to be potent inhibitors of aromatase. Recent research has focused on producing a more metabolically stable aromatase inhibitor by replacing the carbon-sulfur bond at the 7 alpha-position with a carbon-carbon bond. The new inhibitors, 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones (2-4), have alkyl chains of varying length between the steroid and the aryl ring at the 7 alpha-position. The desired targets were synthesized via a 1,6-conjugate addition of the appropriate cuprate to 17 beta-(tert-butyldimethylsiloxy)androsta-4,6-dien-3-one (7). The synthesis also resulted in the formation of the 7 beta-substituted diastereomers (10-11 and 13) as minor products. Initial assignments of the 7 alpha-phenethyl and 7 beta-phenethyl diastereomers were made using highfield 1-D and 2-D NMR studies. The assignment of the diastereomers was confirmed using X-ray crystallography. These compounds were all good inhibitors of aromatase in vitro when assayed using microsomes isolated from human placenta. The 7 alpha-substituted androst-4-ene-3,17-diones (2-4) were effective inhibitors with apparent K(i)s of 13-19 nM. The corresponding 17 beta-hydroxy analogs (8 and 14) and the 7 beta-substituted androstenediones (13 and 16) were less effective inhibitors with apparent K(i)s of 36-44 nM. Thus, a new series of 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones has been synthesized, and the compounds are potent competitive inhibitors of aromatase.
• NICKISH, KLAUS;LAURENT, HENRY, TETRAHEDRON LETT., 29,(1988) N 13, 1533-1536
  作者：NICKISH, KLAUS、LAURENT, HENRY

  DOI：——

  日期：——