16B-羟基雌酮二乙酸酯 | 1247-70-7

• 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: 16B-羟基雌酮二乙酸酯
• 英文名称: 3,16β-diacetoxyestra-1,3,5(10)-trien-17-one
• 英文别名: 3,16β-O-diacetylestrone；3,16β-Diacetoxy-oestra-1,3,5(10)-trien-17-on；3,16β-bis(acetyloxy)-oestra-1,3,5(10)-trien-17-one；Estra-1,3,5(10)-trien-17-one, 3,16-bis(acetyloxy)-, (16beta)-；[(8R,9S,13S,14S,16S)-3-acetyloxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-16-yl] acetate
• CAS: 1247-70-7
• 化学式: C₂₂H₂₆O₅
• 分子量: 370.445
• InChiKey: QZQSENRWYLQIPC-KOVVAJLHSA-N

物化性质

• 熔点：
  148-149 °C
• 沸点：
  500.8±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  16B-羟基雌酮二乙酸酯 在 甲醇 作用下， 反应 7.0h， 生成 3-hydroxy-17β-(2-methoxyethylamino)estra-1,3,5(10)-trien-16-one
  参考文献：
  名称：

  Structure of the adduct of 16α-hydroxyestrone with a primary amine: evidence for the heyns rearrangement of steroidal D-ring α-hydroxyimines

  摘要：

  16-alpha-Hydroxyestrone, a product of estrogen 16-alpha-hydroxylation in humans that is suspected to be implicated in cell transformation, has been found to form stable adducts with nuclear components. The stable covalent adduct formed from 16-alpha-hydroxyestrone with 2-methoxyethylamine via the Heyns rearrangement of the alpha-hydroxyimine was identified as 3-hydroxy-17-beta-(2-methoxyethylamino)estra-1,3,5(10)-trien-16-one. Since the same product was obtained from 16-beta-hydroxyestrone with the amine, the alpha-hydroxyenamine is the most likely intermediate of the Heyns rearrangement. The adduct was fairly stable at 37 C in phosphate buffer (pH 7.4)/methanol (1:1 v/v), while the adduct formed from 16-oxoestradiol was disrupted reversely and completely within 6 hours. The evidence suggests that N-(3-hydroxy-16-oxoestra-1,3,5(10)-trien-17-beta-yl)amine is the partial structure of the stable adducts formed from D-ring alpha-ketol estrogens with proteins.

  DOI：

  10.1016/0039-128x(91)90068-7
• 作为产物：
  描述：

  16-去氢雌二醇二醋酸酯 在 lead(IV) acetate 、 乙酸酐 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 生成 16B-羟基雌酮二乙酸酯
  参考文献：
  名称：

  Novel 17-amino-16-hydroxy steroids of the androstane and oestrane series

  摘要：

  本发明揭示了具有以下化学式I的雄烷和雌烷系列的新型、药理学上有用的17-氨基-16-羟基类固醇，以及其药学上可接受的无毒酸盐，其中：R.sub.1 = H或含有1至6个碳原子的烃基（优选为较低的烷基，如甲基）；R.sub.2 = H或含有1至6个碳原子的烃基（优选为较低的烷基，如甲基）；R.sub.3 = 自由、酯化或醚化的羟基基团；环A包括碳原子6和9具有以下配置之一：其中R.sub.4 = 自由、酯化或醚化的羟基基团；R.sub.5 = O或H(R.sub.7)，其中R.sub.7是自由、酯化或醚化的羟基基团；R.sub.6 = H或甲基；虚线代表4,5-或5,6-位的可选双键；以及这些类固醇的对映体和拉氏体。这些新型化合物具有抗心律失常的特性。

  公开号：

  US04330539A1

文献信息

• Production of 16β-(acetoxy)acetoxy derivatives by reaction of 17-keto steroid enol acetates with lead (IV) acetate
  作者：M Numazawa

  DOI：10.1016/s0039-128x(01)00103-9

  日期：2001.10

  16beta-acetoxy-17-ketones with the lead reagent did not yield the corresponding (acetoxy)acetates. Reaction of the enol acetate 3 with Pb(OCOCD(3))(4) in CD(3)COOD yielded principally the labeled (acetoxy)acetate 10-d(3), which had a CD(3)COOCH(2)COO moiety at C-16beta. In contrast, when the deuterated enol acetate 3-d(3), which was obtained by treatment of the 17-ketone 14 with (CD(3)CO)(2)O in the presence

  用 Pb(OCOCH(3))(4) 处理 3beta-acetoxyandrost-5-en-17-one 及其 5alpha-reduced 类似物 5alpha-androstan-17-one 和醋酸雌酮，1-4 的烯醇乙酸酯在乙酸和乙酸酐中得到先前未报道的产物 16β-（乙酰氧基）乙酰氧基-17-酮 8-10 和 12，产率 9-15%，以及已知的主要产物 16β-乙酰氧基-17-酮 5- 7 和 11。用先导试剂对 16β-乙酰氧基-17-酮进行类似处理没有产生相应的（乙酰氧基）乙酸盐。烯醇乙酸酯 3 与 Pb(OCOCD(3))(4) 在 CD(3)COOD 中的反应主要产生标记的（乙酰氧基）乙酸酯 10-d(3)，其具有 CD(3)COOCH(2)COO C-16beta 的部分。相反，当氘代烯醇乙酸酯 3-d(3) 时，通过在 LDA 存在下用 (CD(3)CO)(2)O 处理
• Novel 17-amino-16-hydroxy steroids of the androstane and oestrane series
  申请人：Akzo nv

  公开号：US04330539A1

  公开（公告）日：1982-05-18

  New and pharmacologically useful 17-amino-16-hydroxy-steroids of the androstane and oestrane series are disclosed having the formula I: ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, wherein: R.sub.1 =H or hydrocarbyl of one to six carbon atoms (preferably lower alkyl, such as methyl); R.sub.2 =H or hydrocarbyl of one to six carbon atoms (preferably lower alkyl, such as methyl); R.sub.3 =a free, esterified or etherified hydroxyl group; ring A inclusive carbon atoms 6 and 9 has one of the following configurations: ##STR2## in which R.sub.4 =a free, esterified or etherified hydroxyl group; R.sub.5 =O or H(R.sub.7), wherein R.sub.7 is a free, esterified or etherified hydroxyl group; R.sub.6 =H or methyl; and the dotted lines represent an optional double bond in 4,5- or 5,6-position; as well as the enantiomers and racemates of these steroids. The novel compounds have antiarrhythmic properties.

  本发明揭示了具有以下化学式I的雄烷和雌烷系列的新型、药理学上有用的17-氨基-16-羟基类固醇，以及其药学上可接受的无毒酸盐，其中：R.sub.1 = H或含有1至6个碳原子的烃基（优选为较低的烷基，如甲基）；R.sub.2 = H或含有1至6个碳原子的烃基（优选为较低的烷基，如甲基）；R.sub.3 = 自由、酯化或醚化的羟基基团；环A包括碳原子6和9具有以下配置之一：其中R.sub.4 = 自由、酯化或醚化的羟基基团；R.sub.5 = O或H(R.sub.7)，其中R.sub.7是自由、酯化或醚化的羟基基团；R.sub.6 = H或甲基；虚线代表4,5-或5,6-位的可选双键；以及这些类固醇的对映体和拉氏体。这些新型化合物具有抗心律失常的特性。
• Alternative synthesis for the preparation of 16<i>α</i>-[¹⁸F]fluoroestradiol
  作者：Hee Seup Kil、Han Yang Cho、Sang Ju Lee、Seung Jun Oh、Dae Yoon Chi

  DOI：10.1002/jlcr.3076

  日期：2013.10

  We have developed a new precursor, 3,17β-O-bis(methoxymethyl)-16β-O-p-nitrobenzenesulfonylestriol (14c) of 16α-[18F]fluoroestradiol ([18F]FES). Although we could not selectively protect the C17 alcohol in the presence of the C16 alcohol, we were able to prepare and chromatographically isolate the desired C16 TBDMS, C17,C3-dimethoxymethyl (diMOM) protected estriol derivative and convert into the ultimate fluorination precursor. The MOM protective group proved to be more quickly removed than the cyclic sulfate group. The di-MOM protective precursor at the C3 and C17 alcohols instead of a cyclic sulfate group shortened hydrolysis time. We prepared three different sulfonate precursors at C16 alcohol. After checking their reactivity in the [18F]fluorination step and considering the stability of the precursors, we obtained the best results with nosylate precursor 14c.

  我们开发了一种新的前体，16α-[18F]氟雌二醇（[18F]FES）的3,17β-O-双（甲氧基甲基）-16β-O-对硝基苯磺酰雌三醇（14c）。尽管我们无法在 C16 醇存在的情况下选择性地保护 C17 醇，但我们能够制备并通过色谱分离所需的 C16 TBDMS、C17,C3-二甲氧基甲基 (diMOM) 保护的雌三醇衍生物，并将其转化为最终的氟化前体。 MOM 保护基团被证明比环状硫酸基团更容易被去除。 C3和C17醇上的二-MOM保护前体代替环状硫酸基团缩短了水解时间。我们在 C16 醇中制备了三种不同的磺酸盐前体。在检查了它们在[18F]氟化步骤中的反应性并考虑了前体的稳定性后，我们用苯磺酸盐前体14c获得了最好的结果。
• Novel 17-amino-16-hydroxy steroids of the androstane and oestrane series and derivatives thereof, processes for their preparation and pharmaceutical compositions
  申请人：AKZO N.V.

  公开号：EP0033561A1

  公开（公告）日：1981-08-12

  New and pharmacologically useful 17-amino-16-hydroxy-steroids of the androstane and oestrane series are disclosed having the formula I: and pnarmaceutically acceptable non-toxic acid addition salts thereof, wherein: R, = H or hydrocarbyl of one to six carbon atoms (preferably lower alkyl , such as methyl); R2 = H or hydrocarbyl of one to six carbon atoms (preferably lower alkyl, such as methyl); R3 = a free, esterified or etherified hydroxyl group; ring A inclusive carbon atoms 6 and 9 has one of the following configurations: in which R4 = a free, esterified or etherified hydroxyl group; R5 = O or H(R7), wherein R7 is a free, esterified or etherified hydroxyl group; R6 = H or methyl; and the dotted lines represent an optional double bond in 4,5- or 5,6-position; as well as the enantiomers and racemates of these steroids. The novel compounds have antiarrhythmic properties.

  本研究公开了具有式 I 的新的药理作用的雄烷和雌烷系列 17-氨基-16-羟基类固醇： 及其药学上可接受的无毒酸加成盐，其中 R，＝H 或一至六个碳原子的烃基（最好是低级烷基，如甲基）； R2 = H 或一至六个碳原子的烃基（最好是低级烷基，如甲基）； R3 = 自由的、酯化的或醚化的羟基； 包含碳原子 6 和 9 的环 A 具有下列构型之一： 其中 R4 = 自由、酯化或醚化羟基； R5 = O 或 H(R7)，其中 R7 是游离的、酯化的或醚化的羟基； R6 = H 或甲基；以及 虚线代表 4,5- 位或 5,6- 位的任选双键； 以及这些类固醇的对映体和外消旋体。 这些新型化合物具有抗心律失常的特性。
• Engelfried; Gibian; Neumann, Arzneimittel-Forschung/Drug Research, 1966, vol. 16, # 11, p. 1518 - 1522
  作者：Engelfried、Gibian、Neumann、Prezewowsky、Schulz、Wiechert

  DOI：——

  日期：——