(4α,5)-epoxy-5α-androstan-3,17-dione | 17503-11-6

• 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: (4α,5)-epoxy-5α-androstan-3,17-dione
• 英文别名: 4α,5α-epoxyandrostane-3,17-dione；androstan-4α,5α-epoxy-3,17-dione；4,5-epoxyandrostane-3,17-dione；4α,5-epoxy-5α-androstane-3,17-dione；4α,5-Epoxy-5α-androstan-3,17-dion；(1S,2R,6S,8S,11R,12S,16S)-2,16-dimethyl-7-oxapentacyclo[9.7.0.02,8.06,8.012,16]octadecane-5,15-dione
• CAS: 17503-11-6
• 化学式: C₁₉H₂₆O₃
• 分子量: 302.414
• InChiKey: LIMBPOMDHZQBJH-KPXRGQPZSA-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：

  (4α,5)-epoxy-5α-androstan-3,17-dione 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 以76%的产率得到5α-hydroxyandrostane-3,17-dione
  参考文献：
  名称：

  Torii, Sigeru; Okumoto, Hiroshi; Nakayasu, Seizo, Chemistry Letters, 1989, p. 1975 - 1978

  摘要：

  DOI：
• 作为产物：
  描述：

  雄烯二酮 生成 (4α,5)-epoxy-5α-androstan-3,17-dione
  参考文献：
  名称：

  HRYCKO, SOPHIA;MORAND, PETER, J. CHEM. SOC. PERKIN TRANS. PT 1,(1990) N1, C. 2899-2904

  摘要：

  DOI：

文献信息

• Diastereoselective epoxidation of olefins by organo sulfonic peracids, II
  作者：R. Kluge、M. Schulz、S. Liebsch

  DOI：10.1016/0040-4020(95)01128-5

  日期：1996.2

  have investigated the behaviour of sulfonic peracids 2in situ generated towards olefins 7a,7b,9,11,14,16,18, allylic and homoallylic alcohols 20,22,24,26,28,30,33 and α,β-unsaturated ketones 35,37,39. Generally, the epoxidation proceeds in a peracid-like manner with greater diastereoselectivity than those by common oxidants. In particular, the epoxidation of Δ4 3-ketosteroids 39a-i led to 4α,5α-epoxides

  我们已经调查磺酸过酸的行为2原位朝向烯烃产生的图7A，7B，9,11,14,16,18，烯丙基和高烯丙基醇20,22,24,26,28,30,33和α，β-不饱和酮35,37,39。通常，环氧化以类似过酸的方式进行，其非对映选择性高于普通氧化剂。特别是，环氧化Δ 4 3-酮类固醇39A-I导致4α，5α环氧化物40A-i的具有显着的高解值。在胆固醇28b的环氧化中也发现了增强的α-选择性。由于反应条件温和，甚至对酸敏感的环氧化物以良好的产率获得了8a，8b，10，12，13，15，17，19。
• Aspects of stereochemistry. Part XIX. Directive effects of remote substituents on the alkaline epoxidation of 3-oxo-Δ⁴-steroids
  作者：H. B. Henbest、W. R. Jackson

  DOI：10.1039/j39670002459

  日期：——

  not contain polar substituents react with alkaline hydrogen peroxide to give 3-oxo-4β,5β-epoxides. Up to 30% of the α-epoxy-ketone is formed when the steroid contains a polar group at C-17 or beyond; this result is discussed in terms of electrostatic interactions between the polar substituent and the anionic transition states. Polar substituents at C-11 show stronger directive effects.

  3-氧代- Δ 4不含有极性取代基-steroids与碱性过氧化氢反应，得到3-氧代- 4β，5β-环氧化物。当类固醇在C-17或更高的位置包含极性基团时，最多会形成30％的α-环氧酮。根据极性取代基和阴离子过渡态之间的静电相互作用来讨论该结果。C-11处的极性取代基显示出较强的指示作用。
• Interactions of thiol-containing androgens with human placental aromatase
  作者：Patrick J. Bednarski、Sidney D. Nelson

  DOI：10.1021/jm00121a037

  日期：1989.1

  androstenedione. The inhibitory activity of 19-SHA may be explained by two independent mechanisms: (1) suicide inactivation of aromatase in the ferrous state; and (2) a direct "hyper-type II" binding to the remaining portion of the cytochrome in the ferric state. A free thiol group was necessary for the suicide inhibitory activity of 19-SHA; time-dependent inactivation of aromatase by 19-(acetylthio)androst-4-ene-3

  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
• Peroxide oxidation of Δ⁴-3-ketosteroids
  作者：Herbert L. Holland、Elly Riemland、Ulrich Daum

  DOI：10.1139/v82-268

  日期：1982.8.1

  Treatment of Δ⁴-3-ketosteroids with tert-buly hydroperoxide in the presence of lithium hydroxide leads to the formation of the corresponding 4β,5β epoxides stereospecifically and in good yield. The stereospecificity of this reaction is explicable in terms of the accepted mechanism for the hydrogen peroxide epoxidation of Δ⁴-3-ketosteroids.The use of aqueous sodium peroxide as oxidant leads to the production of the corresponding Δ⁴-3,6-diones. A mechanism for this reaction is proposed in which the key step is autoxidation of the corresponding deconjugated Δ⁵-3-ketone, produced from the starting material insitu by the action of the reagents. Lithium peroxide does not oxidize androst-4-ene-3,17-dione at C-6, but produces the 4,5 epoxides in low yield together with an A-nor-3,5-secoacid.

  Δ⁴-3-酮类固醇在叔丁基过氧化氢存在下，在氢氧化锂存在下处理，会特异性地形成相应的4β,5β环氧化物，并且收率较高。这种反应的特异性可以通过已接受的氢过氧化物环氧化Δ⁴-3-酮类固醇的机制来解释。使用水过氧化钠作为氧化剂会导致相应的Δ⁴-3,6-二酮的生成。对于这种反应提出了一个机制，其中关键步骤是由试剂的作用在原位产生的相应的去共轭Δ⁵-3-酮类固醇的自氧化。氧化锂不会氧化雄烯-4-烯-3,17-二酮的C-6位，但会产生收率较低的4,5环氧化物，同时伴随着一个A-诺尔-3,5-去氧基酸。
• 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