1,3,5[10]-雌甾三烯-3,16alpha,17beta-三羟基 17-葡糖苷酸 | 7219-89-8

• 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
• 中文名称: 1,3,5[10]-雌甾三烯-3,16alpha,17beta-三羟基 17-葡糖苷酸
• 中文别名: 1,3,5[10]-雌甾三烯-3,16alpha,17beta-三羟基17-葡糖苷酸
• 英文名称: 3,16α-dihydroxy-1,3,5(10)-estratrien-17β-yl-β-D-glucopyranosiduronic acid
• 英文别名: estriol 17β-(β-D-glucuronide)；estriol 17β-β-D-glucuronide；estriol 17-(β-D-glucuronide)；estriol-17β-D-glucoronide；estriol 17-glucuronide；16alpha,17beta-Estriol 17-(beta-D-glucuronide)；(2S,3S,4S,5R,6R)-6-[[(8R,9S,13S,14S,16R,17R)-3,16-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 7219-89-8
• 化学式: C₂₄H₃₂O₉
• 分子量: 464.513
• InChiKey: CZGFLAQOJPXVRV-FLVROIOLSA-N

物化性质

• 沸点：
  738.3±60.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.708
• 拓扑面积：
  157
• 氢给体数：
  6
• 氢受体数：
  9

安全信息

• 安全说明：
  S22,S36
• 危险类别码：
  R20/21/22,R40

反应信息

• 作为反应物：
  描述：

  1,3,5[10]-雌甾三烯-3,16alpha,17beta-三羟基 17-葡糖苷酸 在 β-glucoronidase II 作用下， 以 水 为溶剂， 反应 0.17h， 生成 D-吡喃葡萄糖醛酸 、 雌三醇
  参考文献：
  名称：

  Ogushi, Susumu; Koga, Satoshi; Ito, Kiyoshi, Agricultural and Biological Chemistry, 1986, vol. 50, # 12, p. 3093 - 3100

  摘要：

  DOI：
• 作为产物：
  描述：

  雌三醇 在 sodium hydroxide 、 无水碳酸镉 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 24.0h， 生成 1,3,5[10]-雌甾三烯-3,16alpha,17beta-三羟基 17-葡糖苷酸
  参考文献：
  名称：

  The synthesis of estriol 16- and 17-monoglucuronide from estriol

  摘要：

  An efficient and convenient procedure for the synthesis of estriol 16- and 17-monoglucuronides from estriol is described. This is achieved by the selective protection and deprotection of the hydroxy groups in estriol, Koenigs-Knorr reactions with methyl 1-bromo-1-deoxy-2,3,4-tri-O-acetyl-alpha-D-glucopyranuronate and subsequent hydrolysis. The products have been characterized by proton nuclear magnetic resonance (1H NMR), two-dimensional 1H homonuclear shift-correlated spectra (2D-COSY) and mass spectra. The selective Koenigs-Knorr reaction of the alcoholic hydroxyl group in the presence of a phenolic hydroxyl group is also reported.

  DOI：

  10.1016/0039-128x(93)90001-4

文献信息

• Regiospecificity and Stereospecificity of Human UDP-Glucuronosyltransferases in the Glucuronidation of Estriol, 16-Epiestriol, 17-Epiestriol, and 13-Epiestradiol
  作者：Nina Sneitz、Mikko Vahermo、Johanna Mosorin、Liisa Laakkonen、Donald Poirier、Moshe Finel

  DOI：10.1124/dmd.112.049072

  日期：2013.3

  The glucuronidation of estriol, 16-epiestriol, and 17-epiestriol by the human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A, and 2B was examined. UGT1A10 is highly active in the conjugation of the 3-OH in all these estriols, whereas UGT2B7 is the most active UGT toward one of the ring D hydroxyls, the 16-OH in estriol and 16-epiestriol, but the 17-OH in 17-epiestriol. Kinetic analyses indicated that the 17-OH configuration plays a major role in the affinity of UGT2B7 for estrogens. The glucuronidation of the different estriols by the human liver and intestine microsomes reflects the activity of UGT1A10 and UGT2B7 in combination with the tissues’ difference in UGT1A10 expression. The UGT1A10 mutant 1A10-F93G exhibited much higher V max values than UGT1A10 in estriol and 17-epiestriol glucuronidation, but a significantly lower value in 16-epiestriol glucuronidation. To this study on estriol glucuronidation we have added experiments with 13-epiestradiol, a synthetic estradiol in which the spatial arrangement of the methyl on C18 and the hydroxyl on C17 is significantly different than in other estrogens. In comparison with estradiol glucuronidation, the C13 configuration change decreases the turnover of UGTs that conjugate the 3-OH, but increases it in UGTs that primarily conjugate the 17-OH. Unexpectedly, UGT2B17 exhibited similar conjugation rates of both the 17-OH and 3-OH of 13-espiestradiol. The combined results reveal the strong preference of UGT1A10 for the 3-OH of physiologic estrogens and the equivalently strong preference of UGT2B7 and UGT2B17 for the hydroxyls on ring D of such steroid hormones.

  检查了亚家族 1A、2A 和 2B 的人 UDP-葡萄糖醛酸基转移酶 (UGT) 对雌三醇、16-表三醇和 17-表三醇的葡萄糖醛酸化。 UGT1A10 在所有这些雌三醇中的 3-OH 缀合中具有高度活性，而 UGT2B7 是对 D 环羟基之一（雌三醇和 16-表三醇中的 16-OH）最活跃的 UGT，但 17 中的 17-OH -表三醇。动力学分析表明，17-OH构型在UGT2B7与雌激素的亲和力中起主要作用。人肝和肠微粒体对不同雌三醇的葡萄糖醛酸化反映了UGT1A10和UGT2B7的活性以及组织中UGT1A10表达的差异。 UGT1A10突变体1A10-F93G在雌三醇和17-表三醇葡萄糖醛酸化中表现出比UGT1A10高得多的V max 值，但在16-表三醇葡萄糖醛酸化中表现出显着较低的值。在这项关于雌三醇葡萄糖醛酸化的研究中，我们添加了 13-表雌二醇的实验，这是一种合成雌二醇，其中 C18 上的甲基和 C17 上的羟基的空间排列与其他雌激素显着不同。与雌二醇葡萄糖醛酸化相比，C13构型变化降低了缀合3-OH的UGT的周转率，但增加了主要缀合17-OH的UGT的周转率。出乎意料的是，UGT2B17 表现出与 13-espiestradiol 的 17-OH 和 3-OH 相似的缀合率。综合结果揭示了UGT1A10对生理雌激素的3-OH的强烈偏好，以及UGT2B7和UGT2B17对此类类固醇激素的环D上的羟基的同样强烈的偏好。
• Eudismic analysis of tricyclic sesquiterpenoid alcohols: Lead structures for the design of potent inhibitors of the human UDP-glucuronosyltransferase 2B7
  作者：Ingo Bichlmaier、Mika Kurkela、Antti Siiskonen、Moshe Finel、Jari Yli-Kauhaluoma

  DOI：10.1016/j.bioorg.2007.07.002

  日期：2007.10

  The epimeric tricyclic sesquiterpenoid alcohols globulol, epiglobulol, cedrol, epicedrol, longifolol, and isolongifolol were investigated in their ability to inhibit the recombinant human UDP-glucuronosyltransferase (UGT) 2B7. The stereoisomers displayed rapidly reversible competitive inhibition, which was substrate-independent. Longifolol and its stereoisomer isolongifolol displayed the lowest competitive inhibition constants (K-ic) of 23 and 26 nM, respectively. The K-ic values of cedrol and its epimer epicedrol were 0.15 and 0.21 mu M, those of globulol and epiglobulol were 5.4 and 4.0 mu M, respectively. The diastereomeric alcohols exhibited nearly identical affinities toward UGT2B7 indicating that the spatial arrangement of the hydroxy group had no influence on the dissociation of the enzyme-terpenoid complex. The high affinities stemmed presumably from mere hydrophobic interactions between the hydrocarbon scaffold of the terpenoid alcohol and the binding site of the enzyme. Glucuronidation assays revealed that there were large differences in the rates at which the epimeric alcohols were conjugated. Therefore, the spatial arrangement of the hydroxy group controlled the rate of the UGT2B7-catalyzed reaction. The introduction of a methyl group into the side chain of isolongifolol and longifolol increased the steric hindrance. As a result, the rate of the UGT2B7-catalyzed reaction was decreased by more than 88%. The findings indicated that the rate of the UGT2B7-catalyzed glucuronidation is significantly controlled by stereochemical and steric factors. Considering the high inhibition levels exerted by the tricyclic sesquiterpenoid alcohols, these compounds might serve as valuable lead structures for the design of potent inhibitors for UGT2B7. (c) 2007 Elsevier Inc. All rights reserved.
• Ogushi, Susumu; Koga, Satoshi; Ito, Kiyoshi, Agricultural and Biological Chemistry, 1986, vol. 50, # 12, p. 3093 - 3100
  作者：Ogushi, Susumu、Koga, Satoshi、Ito, Kiyoshi、Makino, Yasutaka、Ando, Makoto、Tsuru, Daisuke

  DOI：——

  日期：——
• The synthesis of estriol 16- and 17-monoglucuronide from estriol
  作者：Wu Yinqiu、Leonard F. Blackwell

  DOI：10.1016/0039-128x(93)90001-4

  日期：1993.10

  An efficient and convenient procedure for the synthesis of estriol 16- and 17-monoglucuronides from estriol is described. This is achieved by the selective protection and deprotection of the hydroxy groups in estriol, Koenigs-Knorr reactions with methyl 1-bromo-1-deoxy-2,3,4-tri-O-acetyl-alpha-D-glucopyranuronate and subsequent hydrolysis. The products have been characterized by proton nuclear magnetic resonance (1H NMR), two-dimensional 1H homonuclear shift-correlated spectra (2D-COSY) and mass spectra. The selective Koenigs-Knorr reaction of the alcoholic hydroxyl group in the presence of a phenolic hydroxyl group is also reported.