4-hydroxyestrone 2-N-acetylcysteine thioether | 178425-19-9

• 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: 4-hydroxyestrone 2-N-acetylcysteine thioether
• 英文别名: (2R)-2-acetamido-3-[[(8R,9S,13S,14S)-3,4-dihydroxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-2-yl]sulfanyl]propanoic acid
• CAS: 178425-19-9
• 化学式: C₂₃H₂₉NO₆S
• 分子量: 447.552
• InChiKey: WNTOFKKVXNANGI-IFYIBNLMSA-N

物化性质

• 沸点：
  692.6±55.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  149
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-hydroxyestrone 2-N-acetylcysteine thioether 在 乙酸酐 作用下， 以 甲醇 、 乙醚 、 氯仿 为溶剂， 反应 0.33h， 生成 N-acetyl-S-<3-hydroxy-4-methoxy-17-oxo-1,3,5(10)-estratrien-2-yl>-L-cysteine 2,3-lactone
  参考文献：
  名称：

  Enzymic and chemical O-methylation of a 4-hydroxyestrone N-acetylcysteine conjugate

  摘要：

  4-Hydroxyestrone N-acetylcysteine conjugate (4-OHE1-2SR) is considered to be an important compound for monitoring the in vivo formation of catechol estrogen quinones, an intermediary in estrogen carcinogenicity. This article describes the selective synthesis of isomeric monomethyl ethers of 4-OHE1-2SR utilizing the formation of a seven-membered ring lactone by dehydration with acetic anhydride. Using these authentic specimens, enzymic and chemical O-methylation were examined. Enzymic O-methylation, using a rat liver cytosolic fraction, of 4-OHE1-2SR gave its 3-methyl ether as the sole product, while preferential O-methylation of 4-hydroxyestrone (4-OHE,) at the C-4 position was confirmed under the same conditions. Methylation of 4-OHE1-2SR with diazomethane gave initially carboxylate methylation, then the corresponding 3-methyl ether almost exclusively, while methylation of 4-OHE1 also gave its 3-methyl ether preferentially. However, much more rapid formation of the 3-methyl ether was observed with 4-OHE1-2SR than with 4-OHE1 itself. These results show that the hydroxy group at the C-3 position of 4-OHE1-2SR is more reactive than that at the C-4 position, both chemically and enzymatically. (Steroids 63:672-677, 1998) (C) 1998 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(98)00080-4
• 作为产物：
  描述：

  2-(N-乙基-3-甲基-4-亚硝基苯胺基)乙醇 在 盐酸 、 sodium periodate 、 溶剂黄146 、 锌 作用下， 以 溶剂黄146 为溶剂， 反应 0.55h， 生成 4-hydroxyestrone 2-N-acetylcysteine thioether
  参考文献：
  名称：

  邻苯二酚雌激素的N-乙酰半胱氨酸结合物的合成。

  摘要：

  描述了2-羟基雌酮（2-OHE1）和4-羟基雌酮（4-OHE1）的N-乙酰半胱氨酸缀合物的合成。雌酮2,3-醌与N-乙酰半胱氨酸的反应提供了2-OHE1及其C-4和C-1硫醚共轭物，比例为1：1，而雌酮3,4-醌与N-乙酰半胱氨酸的比例为4- OHE1及其C-2硫醚共轭物是唯一产品。通过检查NMR光谱，化学衍生化（甲基化和乙酰化），并与4-溴雌酮2,3-醌或2-溴雌酮3,4-醌对N-乙酰半胱氨酸的反应性进行比较来表征它们的结构。

  DOI：

  10.1016/0039-128x(95)00232-f

文献信息

• Synthesis and Structure Elucidation of Estrogen Quinones Conjugated with Cysteine, <i>N</i>-Acetylcysteine, and Glutathione
  作者：Kai Cao、Douglas E. Stack、Ragulan Ramanathan、Michael L. Gross、Eleanor G. Rogan、Ercole L. Cavalieri

  DOI：10.1021/tx9702291

  日期：1998.8.1

  Catechol estrogen quinones (CE-Q) have been implicated as ultimate carcinogenic metabolites in estrogen-induced carcinogenesis. CE-Q may covalently bind to DNA to initiate cancer. These quinones can also be conjugated with glutathione, a reaction that prevents damage to DNA by CE-Q. The glutathione conjugates are then catabolized through mercapturic acid biosynthesis to cysteine and N-acetylcysteine conjugates. This may be the most important detoxification pathway of CE-Q. The chemical synthesis and characterization of these conjugates are the first essential steps to better understand their function in biological systems. Eighteen conjugates were synthesized by reaction of estrone-3,4-quinone (E-1-3,4-Q), estradiol-3,4-quinone (E-2-3,4-Q), estrone-2,3-quinone (E-1-2,3-Q), or estradiol-2,3-quinone (E-2-2,3-Q) with various sulfur: nucleophiles, RSH, in which R is the cysteine, N-acetylcysteine, or glutathione moiety. Reactions of E-1-3,4-Q and E-2-3,4-Q produce regiospecifically 4-OHE1-2-SR and 4-OHE2-2-SR, respectively, in almost quantitative yield. E-1-2,3-Q and E-2-2,3-Q react regioselectively and quantitatively to form S-OHE1(E-2)-1-SR and 8-OHE1(E-2)-4-SR, in which the l-isomers are always the major products. The ratio between 1 and 4 isomers is 3.5 for cysteine, 2.7 for N-acetylcysteine, and 2.5 for glutathione. The synthesized conjugates will be used as standards in the identification of these compounds formed in biological systems.