3-methoxy-estra-1,3,5(10)-trien-6β-ol | 134223-98-6

• 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: 3-methoxy-estra-1,3,5(10)-trien-6β-ol
• 英文别名: (6R,8S,9S,13S,14S)-3-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-6-ol
• CAS: 134223-98-6
• 化学式: C₁₉H₂₆O₂
• 分子量: 286.414
• InChiKey: UQDQFDQWBZXDQR-FDMITFGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  三氧化硫吡啶 、 3-methoxy-estra-1,3,5(10)-trien-6β-ol 反应 1.0h， 以25 mg的产率得到pyridinium 3-methoxy-estra-1,3,5(10)-trien-6β-yl sulfate
  参考文献：
  名称：

  Synthesis and mechanism of hydrolysis of estrogen 6-sulfates: Model compounds for demonstrating the carcinogenesis of estrogen

  摘要：

  To investigate the carcinogenesis of estrogen with respect to the chemical behavior of estrogen 6-sulfates, two epimeric 6-sulfates, pyridinium 3-methoxyestra-1,3,5(10)-trien-6 alpha-yl (8) and -6 beta-yl (11) sulfates, were synthesized as the model compounds, and their chemical reactivities were examined. These sulfates were shown to be highly reactive: in water, they were readily and quantitatively converted to a common product mixture, composed of 3-methoxyestra-1,3,5(10)-trien-6 alpha-ol (6) and -6 beta-ol (9) in an almost constant product ratio, with a predominant yield of the latter. The hydrolysis of both sulfates 8 and 11 proceeded in first-order kinetics with half-lives of 1.1 and 1.5 minutes, respectively. When the sulfates were hydrolyzed in 18O-water, the heavy-oxygen atom was shown to be incorporated quantitatively into the C-6 position of the products. These results demonstrate that estrogen 6-sulfates generate a highly reactive benzylic (C-6) carbocation in an aqueous solution, suggesting that the sulfates can act as carcinogens.

  DOI：

  10.1016/0039-128x(91)90078-a
• 作为产物：
  描述：

  pyridinium 3-methoxy-estra-1,3,5(10)-trien-6β-yl sulfate 在 水 作用下， 以 二甲基亚砜 为溶剂， 生成 3-methoxy-estra-1,3,5(10)-trien-6β-ol
  参考文献：
  名称：

  Synthesis and mechanism of hydrolysis of estrogen 6-sulfates: Model compounds for demonstrating the carcinogenesis of estrogen

  摘要：

  To investigate the carcinogenesis of estrogen with respect to the chemical behavior of estrogen 6-sulfates, two epimeric 6-sulfates, pyridinium 3-methoxyestra-1,3,5(10)-trien-6 alpha-yl (8) and -6 beta-yl (11) sulfates, were synthesized as the model compounds, and their chemical reactivities were examined. These sulfates were shown to be highly reactive: in water, they were readily and quantitatively converted to a common product mixture, composed of 3-methoxyestra-1,3,5(10)-trien-6 alpha-ol (6) and -6 beta-ol (9) in an almost constant product ratio, with a predominant yield of the latter. The hydrolysis of both sulfates 8 and 11 proceeded in first-order kinetics with half-lives of 1.1 and 1.5 minutes, respectively. When the sulfates were hydrolyzed in 18O-water, the heavy-oxygen atom was shown to be incorporated quantitatively into the C-6 position of the products. These results demonstrate that estrogen 6-sulfates generate a highly reactive benzylic (C-6) carbocation in an aqueous solution, suggesting that the sulfates can act as carcinogens.

  DOI：

  10.1016/0039-128x(91)90078-a

文献信息

• Reaction of Adenine with 6-Hydroxyestrogen 6-Sulfates: Model Compounds to Demonstrate Carcinogenesis by Estrogen.
  作者：Shinji ITOH、Akihiro YAMAUCHI、Yoshimi ITOH、Hidetoshi TAKAGI、Itsuo YOSHIZAWA

  DOI：10.1248/cpb.44.1754

  日期：——

  To examine carcinogenesis by estrogens, we investigated the reactivity of 6-hydroxyestrogen 6-sulfates. Two epimeric 6-sulfates, pyridinium 3-methoxyestra-1, 3, 5(10)-trien-6α-yl sulfate (1) and its 6β-isomer (2), were synthesized as model compounds and reacted with adenine under mild conditions to give two common products in the ratios of approximately 3 : 1 and 5 : 1, respectively. The major product was identified as N6-[3-methoxyestra-1, 3, 5(10)-trien-6β-yl] adenine (10), accompanied with its 6α-isomer (9), by comparison with synthetic specimens. These results imply that, in the metabolism of naturally occurring estrogens, hydroxylation at the C6-position and subsequent sulfoconjugation of the benzylic hydroxyl group may produce sulfates which react with DNA to initiate carcinogenesis.

  为了研究雌激素的致癌作用，我们研究了6-羟基雌激素6-硫酸盐的反应性。两种外消旋6-硫酸盐，即吡啶鎓3-甲氧基雌甾-1,3,5(10)-三烯-6α-基硫酸盐（1）及其6β-异构体（2）被合成为模型化合物，并在温和条件下与腺嘌呤发生反应，分别产生两种常见产物，比例约为3：1和5：1。通过与合成样品进行比较，主要产物被确定为N6-[3-甲氧基雌甾-1,3,5(10)-三烯-6β-基]腺嘌呤（10），并伴有其6α-异构体（9）。这些结果表明，在天然雌激素的代谢过程中，C6位羟基化以及随后苯基羟基的硫酸化可能会产生硫酸盐，硫酸盐与DNA发生反应，从而引发癌症。