3,3-ethylenedioxy-5(10)-epoxy-estr-9(11)-ene-17-one | 39931-88-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 英文名称: 3,3-ethylenedioxy-5(10)-epoxy-estr-9(11)-ene-17-one
• 英文别名: 3-(ethylenedioxy)estra-5β,10β-epoxy-9(11)-ene-17-one；3,3-(ethylenedioxy)-5β,10β-epoxyestra-9(11)-ene-17-one；3,3-etheylenedioxy-5(10)-β-epoxyestra-9(11)-ene-17-one；3,3,17,17-ethylenedioxy-5(10)-β-epoxy-estr-9(11)-ene；3,3-ethylenedioxy-5-β,10-β-epoxyestr-9(11)-ene-17-one；3,3-ethylenedioxy-5(10)-β-epoxy-estr-9(11)-ene-17-one；3,3-(Ethylenedioxy)-5beta,10beta-epoxyestra-9(11)-en-17-one；(1'S,5'S,9'S,10'S,13'S)-5'-methylspiro[1,3-dioxolane-2,15'-18-oxapentacyclo[11.4.1.01,13.02,10.05,9]octadec-2-ene]-6'-one
• CAS: 39931-88-9
• 化学式: C₂₀H₂₆O₄
• 分子量: 330.424
• InChiKey: BAMMJXIMVWLRCU-BBTQSVATSA-N

物化性质

• 沸点：
  499.1±45.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  48.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3-ethylenedioxy-5(10)-epoxy-estr-9(11)-ene-17-one 在 盐酸 、 copper(l) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.67h， 生成 11α-cyclohexyl-estra-4,9-diene-3,17-dione
  参考文献：
  名称：

  Hydrolytic behavior of 5α-hydroxy-11β- and 5β-hydroxy-11α-substituted 19-norsteroids

  摘要：

  Teutsch G. and Belanger A. treated 5alpha,10alpha epoxides with Grignard-reagents catalyzed by copper(l) ions. The reaction with steroidal epoxides proceeded with complete regio- and stereospecificity, leading exclusively to the 11beta-substituted compounds. According to our synthetic strategy, the 5, 10 epoxide isomers were not separated; instead, the pure 11beta, and in some cases, 11alpha-substituted molecules were isolated after the conjugate addition of the Grignard-reagents, followed by deketalization and dehydration. Surprisingly, appearance of a third compound was generally observed beside the expected deprotected products, and this compound turned out to have a 3-keto-5(10),9(11) structural unit. Starting from pure 3-ethylenedioxy-5alpha,10alpha-epoxy-estr-9(11)-ene-17-one and 3-ethylenedioxy-5beta,10beta-epoxy-estr-9(11)-ene-17-one, four model compounds were synthesized (11alpha- and 11beta-{4-[1,1-(ethylenedioxy)-ethyl]phenyl}-estra-, as well as 11alpha- and 11beta-cyclohexyl-estra-derivatives) to study the process of deprotection and dehydration. 3-keto-5(10),9(11)-derivatives were found to form after deketalization and dehydration only from 11alpha-substituted derivatives, while 11beta-derivatives resulted in only the expected 3-keto-5,9-diene structure. After observing this remarkable difference between the behavior of 11alpha-, 11beta-substituted isomers we decided to take a closer look at the processes of deketalization and dehydration. In order to carry out the hydrolysis under mild conditions, pyridinium paratoluenesulfonate, a weakly acidic salt, was applied. All the intermediate products observed by TLC were isolated. The outcome of the deprotection and elimination reactions can be rationalized by two factors: conjugation of olefins (with the 3-oxo-group or the 11-phenyl group) and orientation of groups to be eliminated. (C) 2003 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2003.07.003
• 作为产物：
  描述：

  3-缩酮 在 吡啶 、 双氧水 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以68%的产率得到(5alpha,10alpha)-5,10-环氧-雌甾-9(11)-烯-3,17-二酮环3-(1,2-乙二基缩醛)
  参考文献：
  名称：

  荧光标记的甾体抗雌激素的设计与合成

  摘要：

  亮点荧光标记的 11 取代雌二醇衍生物的聚合合成。最终产品显示出与母体荧光团一致的特性。结构特征区分物理化学特性和受体结合。摘要 制备了一组 11°-(4-氧苯基)雌二醇衍生物作为评估雌激素受体的潜在荧光成像剂。这些化合物的设计基于 11°-[4-(二甲基乙氧基)苯基]雌二醇 (RU39411) 作为雌激素受体 (ER) 拮抗剂的既定亲和力和选择性。5-(二甲氨基)萘-1-磺酰基(丹磺酰基)和7-硝基苯并[c][1,2,5]恶二醇-4-基(NBD)部分是根据它们的荧光和物理化学性质选择的。开发了一种收敛合成，最终在 [3+2] 铜 (I) 辅助的炔烃-叠氮化物环加成偶联中合成了甾体和荧光成分。中间体和最终产品的产率很高，类固醇成分的结构变化将允许评估 ER 亲和力和选择性。

  DOI：

  10.1016/j.steroids.2019.02.013

文献信息

• First synthesis and characterization for the stereoisomers of Ulipristal acetate
  作者：Yi Zhao、Xiaolong Li、Hong Liu、Yongguo Yu、Li Hai、Li Guo、Yong Wu

  DOI：10.1016/j.steroids.2014.12.009

  日期：2015.3

  The three stereoisomers, 11α,17α-isomer I, 11α,17β-isomer II and 11β,17β-isomer III are related substances of the selective progesterone receptor modulator Ulipristal acetate. Herein, we presented an efficient and practical synthesis approach to deliver these three stereoisomers for the first time, and also confirmed the structure of the key intermediate 5a by single-crystal X-ray analysis. Our research

  三种立体异构体，11α,17α-异构体 I、11α,17β-异构体 II 和 11β,17β-异构体 III 是选择性孕酮受体调节剂醋酸乌利司他的相关物质。在此，我们首次提出了一种高效实用的合成方法来传递这三种立体异构体，并通过单晶 X 射线分析确认了关键中间体 5a 的结构。我们的研究将为有机化学家研究醋酸乌利司他的杂质谱提供巨大帮助。
• Novel method and intermediates for preparing 19-norsteroid compounds
  申请人：Aventis Pharma S.A.

  公开号：US20040229853A1

  公开（公告）日：2004-11-18

  The subject of the invention is a method for preparing compounds of general formula (I): 1 in which A, Z, R 3 are as defined in the description, and the intermediate compounds for carrying out this method.

  本发明的主题是一种制备一般式(I)化合物的方法：其中A、Z、R3如描述中所定义，并用于执行该方法的中间化合物。
• The Synthesis of 17α-Methyl-11β-arylestradiol:  Large-Scale Application of the Cerium (III)-Mediated Alkylation of a Ketone
  作者：John Patrick Larkin、Christian Wehrey、Philippe Boffelli、Henri Lagraulet、Guy Lemaitre、Alban Nedelec、Denis Prat

  DOI：10.1021/op010051w

  日期：2002.1.1

  a cuprate generated catalytically from the related Grignard reagent. The A-ring was aromatized by a mixture of acetyl bromide and acetic anhydride. This reaction was optimized by a Design Of Experiments carried out on an automated workstation. The advantages and limits of this approach are discussed. The last step consisted of the stereospecific alkylation of the 17-ketone by methylmagnesium bromide

  17α-Methyl-11β-arylestradiol (17α-methyl-11β-(4-(2-(1-piperidinyl)ethoxy)phenyl)estra-1,3,5(10)-triene-3,17β-diol) 是一种Aventis Pharma 开发的用于治疗骨质疏松症的新分子。它是由去甲甾体中间体亚乙基萜酮（3,3-ethylenedioxyestra-5(10)-9(11​​)-diene-17-one）在中试工厂规模生产的。5(10)-烯烃的立体选择性环氧化是通过过氧化氢和六氯丙酮进行的，这是测试系统中选择性最高的。11β-芳基附属物作为由相关格氏试剂催化生成的铜酸盐引入。A-环被乙酰溴和乙酸酐的混合物芳构化。该反应通过在自动化工作站上进行的实验设计进行了优化。讨论了这种方法的优点和局限性。最后一步由甲基溴化镁和脱水三氯化铈对 17-酮的立体有择烷基化组成。药物物质结晶为水合物（过
• NOVEL METHOD AND INTERMEDIATES FOR PREPARING 19-NORSTEROID COMPOUNDS
  申请人：Prat Denis

  公开号：US20110046402A1

  公开（公告）日：2011-02-24

  The subject of the invention is a method for preparing compounds of general formula (I): in which A, Z, R 3 are as defined in the description, and the intermediate compounds for carrying out this method.

  本发明的主题是一种制备一般式（I）化合物的方法：其中A，Z，R3如描述中所定义，并用于执行该方法的中间化合物。
• Synthesis and preliminary evaluation steroidal antiestrogen–geldanamycin conjugates
  作者：J. Adam Hendricks、Robert N. Hanson、Michael Amolins、John M. Mihelcic、Brian S. Blagg

  DOI：10.1016/j.bmcl.2013.03.116

  日期：2013.6

  Three novel steroidal antiestrogen-geldanamycin conjugates were prepared using a convergent strategy. The antiestrogenic component utilized the 11 beta-(4-functionalized-oxyphenyl) estradiol scaffold, while the geldanamycin component was derived by replacement of the 17-methoxy group with an appropriately functionalized amine. Ligation was achieved in high yield using azide alkyne cyclization reactions. Evaluation of the products against two breast cancer cell lines indicated that the conjugates retained significant antiproliferative activity. (C) 2013 Published by Elsevier Ltd.