3-methoxyestra-1,3,5(10)-trien-6-one | 22837-97-4

• 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: 3-methoxyestra-1,3,5(10)-trien-6-one
• 英文别名: (8S,9S,13S,14S)-3-methoxy-13-methyl-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-6-one
• CAS: 22837-97-4
• 化学式: C₁₉H₂₄O₂
• 分子量: 284.398
• InChiKey: GEBBJQICICCQGH-RRIFGTCXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 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：

  3-methoxyestra-1,3,5(10)-trien-6-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.67h， 生成 pyridinium 3-methoxy-estra-1,3,5(10)-trien-6α-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：

  3-acetoxyestra-1,3,5(10)-triene 在 氢氧化钾 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 生成 3-methoxyestra-1,3,5(10)-trien-6-one
  参考文献：
  名称：

  芳香类固醇。第二部分 某些oestra-1,3,5（10）-三烯的三氧化铬氧化

  摘要：

  已经研究了改变芳基取代基的位置和性质对三氧化铬氧化oestra-1,3,5（10）-三烯的影响。讨论了C-6酮基的去屏蔽作用。

  DOI：

  10.1039/j39690001234

文献信息

• Aromatic steroids. Part II. Chromium trioxide oxidation of some oestra-1,3,5(10)-trienes
  作者：R. C. Cambie、Valerie F. Carlisle、C. J. Le Quesne、T. D. R. Manning

  DOI：10.1039/j39690001234

  日期：——

  The effect of varying the position and nature of aryl substituents on the oxidation of oestra-1,3,5(10)-trienes with chromium trioxide has been examined. The deshielding effect of a C-6 keto-group is discussed.

  已经研究了改变芳基取代基的位置和性质对三氧化铬氧化oestra-1,3,5（10）-三烯的影响。讨论了C-6酮基的去屏蔽作用。
• 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。
• Synthesis and mechanism of hydrolysis of estrogen 6-sulfates: Model compounds for demonstrating the carcinogenesis of estrogen
  作者：Takagi Hidetoshi、Komatsu Ken-ichi、Yoshizawa Itsuo

  DOI：10.1016/0039-128x(91)90078-a

  日期：1991.4

  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.