4,5-epoxyandrostane-3,17-dione | 77057-73-9

• 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: 4,5-epoxyandrostane-3,17-dione
• 英文别名: 4,5-epoxyandrosta-3,17-dione；(1S,2R,11R,12S,16S)-2,16-dimethyl-7-oxapentacyclo[9.7.0.02,8.06,8.012,16]octadecane-5,15-dione
• CAS: 77057-73-9
• 化学式: C₁₉H₂₆O₃
• 分子量: 302.414
• InChiKey: LIMBPOMDHZQBJH-SOJMQHQVSA-N

物化性质

• 沸点：
  444.0±45.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  46.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-epoxyandrostane-3,17-dione 在 三氟化硼乙醚 作用下， 以 苯 为溶剂， 反应 19.0h， 以47%的产率得到福美司坦
  参考文献：
  名称：

  含硫醇的雄激素与人胎盘芳香化酶的相互作用。

  摘要：

  合成并研究了一系列硫醇雄激素，以表征对抑制芳香化酶重要的结构特征。雄烯二酮与2个α-，10个β-或19个位置的硫醇基团的类似物引起人类胎盘芳香化酶的时间依赖性抑制。当将它们的KI和kcat值与4-羟基雄烷-4-烯-3,17-二酮（4-OHa）和10β-炔丙基4-烯-3,17-二酮（PED）的KI和kcat值进行比较时，硫醇雄激素10β-巯基雌二醇-4-烯-3,17-二酮（10β-SHnorA）被证明是最有效的自杀底物。然而，19-巯基和4-烯-3-烯-3,17-二酮（19-SHA）是最好的全能抑制剂。除19-SHA以外的所有化合物均具有正常的I P-450差异光谱以及部分纯化/增溶的人胎盘芳香酶。该系列化合物的Ks值与时间和浓度依赖性抑制实验确定的KI值进行了定性比较。19-SHA诱导了Soret在380和474 nm处的分裂峰，这表明19-硫醇盐直接结合到芳香化酶的三价铁上。这种结合可以

  DOI：

  10.1021/jm00121a037
• 作为产物：
  描述：

  雄烯二酮 在 sodium hydroxide 、 双氧水 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 4,5-epoxyandrostane-3,17-dione
  参考文献：
  名称：

  Synthesis of haptens for use in immunoassays of .DELTA.4-3-ketosteroids.

  摘要：

  为了开发特异性和灵敏度高的免疫检测，合成了类雄性激素、11β-羟基类雄性激素、肾上腺素、孕酮、17α-羟基孕酮、皮质酮、11-脱氧皮质酮和21-脱氧皮质醇的新型羧基衍生物。Δ4-3-酮类固醇的4-羧甲基硫和4-羧乙基硫衍生物的制备是通过在碱催化下，分别用巯基醋酸和巯基丙酸对4, 5-环氧化物进行开环反应来实现的。同时，也制备了这些羧基类固醇的N-琥珀酰亚胺酯。

  DOI：

  10.1248/cpb.30.202

文献信息

• 4-amino androstendione derivatives and process for their preparation
  申请人：Farmitalia Carlo Erba, S.p.A.

  公开号：US04757061A1

  公开（公告）日：1988-07-12

  The invention discloses 4-substituted androstendione derivatives of the following formula (I) ##STR1## wherein R is amino or substituted amino or azido, one of R.sub.1 and R.sub.2 is hydrogen and the other is hydrogen, alkyl, alkenyl or alkynyl, and (x) and (y) are each, independently, a single bond or a double bond. The compounds of formula (I) are useful aromatase inhibitors.

  该发明揭示了以下式（I）的4-取代雄烯二酮衍生物： 其中R是氨基或取代氨基或偶氮基，R.sub.1和R.sub.2中的一个是氢，另一个是氢、烷基、烯基或炔基，（x）和（y）各自独立地是单键或双键。式（I）的化合物是有用的芳香化酶抑制剂。
• Practical Preparation of Diosphenols by Ring Opening of α,β-Epoxyketones Catalyzed by Silica Gel Supported Acids
  作者：Yuefei Hu、Rui Zhu、Lixin Xing、Xinyan Wang、Chuanjie Cheng、Bo Liu

  DOI：10.1055/s-2007-985584

  日期：——

  The mixed acid (H 2 SO 4 -HOAc) catalyzed ring opening of α,β-epoxyketone was the most used method for the preparation of diosphenols, but it seriously suffered from poor yields and -tedious workup operations. By using silica gel supported mixed acid (H 2 SO 4 -HOAc), a variety of α,β-epoxyketones were converted into the corresponding diosphenols in unprecedented high yields within a few minutes.

  混酸(H 2 SO 4 -HOAc)催化α,β-环氧酮开环是制备二酚类化合物最常用的方法，但其收率低，后处理操作繁琐。通过使用硅胶负载的混合酸（H 2 SO 4 -HOAc），各种α,β-环氧酮在几分钟内以前所未有的高产率转化为相应的二酚。
• Synthesis and evaluation of a new series of mechanism-based aromatase inhibitors
  作者：D. Lesuisse、J. F. Gourvest、C. Hartmann、B. Tric、O. Benslimane、D. Philibert、J. P. Vevert

  DOI：10.1021/jm00087a013

  日期：1992.5

  A series of new 4-(alkylthio)-substituted androstenedione analogues was designed as potential suicide inhibitors of aromatase on the basis of mechanistic considerations on the mode of action of the enzyme. Their synthesis and biological evaluation are described. Among the most interesting are the 4-[(difluoromethyl)thio]-, 4-[(fluoromethyl) thio]-, and 4-[(chloromethyl)thio]androstenediones 12,13, and 14 with respective IC50's of 2.7,0.8, and 0.94-mu-M. Compound 12 was a reversible inhibitor of aromatase while compounds 13 and 14 displayed time-dependent kinetics of inhibition with respective K(I)'s and half-times of inactivation of 30 nM and 3.75 min for 13 and 30 nM and 3 min for 14. The inhibition of aromatase by 14 was NADPH-dependent, and was protected by the presence of substrate (0.5-1-mu-M), while beta-mercaptoethanol (0.5 mM) failed to protect the enzyme from inactivation. Dialysis failed to reactivate aromatase previously inactivated by 14. The mechanistic implications of these findings are
• Selective Epoxidation of Olefins by Perfluoro-<i>cis</i>-2,3-dialkyloxaziridines¹
  作者：Alberto Arnone、Darryl D. DesMarteau、Barbara Novo、Viacheslav A. Petrov、Massimo Pregnolato、Giuseppe Resnati

  DOI：10.1021/jo961196h

  日期：1996.1.1

  Alkyl-substituted olefins are epoxidized by perfluoro-cis-2,3-dialkyloxaziridines under particularly mild conditions. Electron deficient substrates (e.g, alpha,beta-enones) can also be epoxidized, and the more electron poor the double bond is, the more severe the reactions conditions become. The epoxidation is chemoselective (secondary alcohols and their ethers do not interfere), site selective (the monoepoxide of a diene can be obtained), and stereoselective (cis-alkenes afford cis-epoxides). Various complex and polyfunctional substrates of natural origin (monoterpenes, sesquiterpenes, steroids) have been transformed effectively.
• Aromatase inhibitors. Synthesis and biological activity of androstenedione derivatives
  作者：David A. Marsh、Harry J. Brodie、Wesley Garrett、Chon Hwa Tsai-Morris、Angela M. H. Brodie

  DOI：10.1021/jm00383a017

  日期：1985.6

  The synthesis and biological evaluation of androstenedione derivatives as inhibitors of estrogen biosynthesis are described. The results show that 4-hydroxy analogues are among the most potent in vitro inhibitors of the series. Esterification of the 4-hydroxy steroids generally reduced activity. Further conjugation of the 3-keto 4-ene system to give 4-hydroxy-4,6-androstadiene-3,17-dione caused more rapid inactivation of aromatase in rat ovarian microsomes than 4-hydroxyandrostenedione. Some compounds exhibited differences in activity when tested for inhibition of human placental microsomes vs. rat ovarian microsomes. The 4-hydroxyandrostenedione derivatives and their nonbulky esters were generally more potent in vitro and in vivo inhibitors than other substituted steroids in the series. Several of the synthesized compounds markedly reduce (50-81%) estrogen levels in rats on proestrus and/or had antifertility action. To date, none of the compounds surpassed the in vivo inhibitory action of 4-hydroxy-4-androstene-3,17-dione or its 4-acetate derivative.