pyridinium 3-methoxy-estra-1,3,5(10)-trien-6α-yl sulfate | 134223-97-5

• 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: pyridinium 3-methoxy-estra-1,3,5(10)-trien-6α-yl sulfate
• 英文别名: pyridinium 3-methoxyestra-1,3,5(10)-trien-6α-yl sulfate；[(6S,8S,9S,13S,14S)-3-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-6-yl] hydrogen sulfate;pyridine
• CAS: 134223-97-5
• 化学式: C₅H₅N*C₁₉H₂₆O₅S
• 分子量: 445.58
• InChiKey: YHPPWIAASWYKDY-UVKBRFDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.34
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  94.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  pyridinium 3-methoxy-estra-1,3,5(10)-trien-6α-yl sulfate 在 盐酸 作用下， 以 四氢呋喃 、 phosphate buffer 、 二甲基亚砜 为溶剂， 反应 0.83h， 生成 N⁶-[3-methoxyestra-1,3,5(10)-trien-6β-yl]adenine
  参考文献：
  名称：

  Identification of Estrogen-Modified Nucleosides from Calf Thymus DNA Reacted with 6-Hydroxyestrogen 6-Sulfates

  摘要：

  Two estrogen sulfates, pyridinium 3-methoxyestra-1,3,5(10)-trien-6 alpha-yl sulfate (3MeE-6 alpha-S) and its GP-isomer (3MeE-6 beta-S), synthesized as model compounds to demonstrate the carcinogenesis of estrogen, were found to react with calf thymus DNA to produce steroid-modified DNA adducts. Digestion of the DNA by nuclease P1 and phosphodiesterase I followed by alkaline phosphatase gave a deoxyribonucleoside fraction, of which N-2-[3-methoxyestra-1,3,5( 10)-trien-6 alpha-yl]deoxyguanosine, N-2-[3-methoxyestra-1,3,5( 10)-trien-6 beta-yl]deoxyguanosine, N-6-[3-methoxyestra-1,3,5(10)-trien-6 alpha-yl]deoxyadenosine, and N-6-[3-methoxyestra-1,3,5(10)trien-6 alpha-yl]deoxyadenosine (identified as a base adduct) were identified using HPLC by comparing them with authentic specimens prepared by reacting dG; and dA with both sulfates. No steroid-dC adduct was detected in the digestion products of the DNA adduct, although dC reacted with the sulfates to form N-4-[3-methoxyestra-1,3,5(10)-trien-G beta-yl] deoxycytidine, These results mean that estrogen B-sulfate has an ability to modify DNA via the amino group of a guanine or adenine residue in DNA. The present studies imply that a sequential metabolism (hydroxylation and sulfation) at the Cs-position of the estrogen molecule causes damage to DNA.

  DOI：

  10.1021/tx9800957
• 作为产物：
  描述：

  17-去氧基雌二醇 在 吡啶 、 3,5-二甲基吡唑 、 chromium(VI) oxide 、 sodium hydroxide 、 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 9.17h， 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

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。
• Identification of Estrogen-Modified Nucleosides from Calf Thymus DNA Reacted with 6-Hydroxyestrogen 6-Sulfates
  作者：Shinji Itoh、Toshiaki Hirai、Yukari Totsuka、Hidetoshi Takagi、Yumiko Tashiro、Koji Wada、Keiji Wakabayashi、Shinya Shibutani、Itsuo Yoshizawa

  DOI：10.1021/tx9800957

  日期：1998.11.1

  Two estrogen sulfates, pyridinium 3-methoxyestra-1,3,5(10)-trien-6 alpha-yl sulfate (3MeE-6 alpha-S) and its GP-isomer (3MeE-6 beta-S), synthesized as model compounds to demonstrate the carcinogenesis of estrogen, were found to react with calf thymus DNA to produce steroid-modified DNA adducts. Digestion of the DNA by nuclease P1 and phosphodiesterase I followed by alkaline phosphatase gave a deoxyribonucleoside fraction, of which N-2-[3-methoxyestra-1,3,5( 10)-trien-6 alpha-yl]deoxyguanosine, N-2-[3-methoxyestra-1,3,5( 10)-trien-6 beta-yl]deoxyguanosine, N-6-[3-methoxyestra-1,3,5(10)-trien-6 alpha-yl]deoxyadenosine, and N-6-[3-methoxyestra-1,3,5(10)trien-6 alpha-yl]deoxyadenosine (identified as a base adduct) were identified using HPLC by comparing them with authentic specimens prepared by reacting dG; and dA with both sulfates. No steroid-dC adduct was detected in the digestion products of the DNA adduct, although dC reacted with the sulfates to form N-4-[3-methoxyestra-1,3,5(10)-trien-G beta-yl] deoxycytidine, These results mean that estrogen B-sulfate has an ability to modify DNA via the amino group of a guanine or adenine residue in DNA. The present studies imply that a sequential metabolism (hydroxylation and sulfation) at the Cs-position of the estrogen molecule causes damage to DNA.
• 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.