dl-Δ⁴-androstene-3,17-dione | 63-05-8

• 物质功能分类: 分析化学 - 标准品 - 中药标准品
• 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: dl-Δ⁴-androstene-3,17-dione
• 英文别名: rac-androst-4-ene-3,17-dione；Androst-4-en-3,17-dion, dl-Δ⁴-Androsten-3,17-dion；(8alpha,9beta,10alpha,13alpha,14beta)-Androst-4-ene-3,17-dione；(8S,9R,10S,13R,14R)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 63-05-8；571-45-9；571-46-0；846-47-9；4860-73-5；5144-25-2；18485-76-2；23633-11-6；41143-27-5；79732-29-9
• 化学式: C₁₉H₂₆O₂
• 分子量: 286.414
• InChiKey: AEMFNILZOJDQLW-BQUOXIOCSA-N

物化性质

• 熔点：
  170-171 °C(lit.)
• 比旋光度：
  D30 +199° (in chloroform)
• 沸点：
  368.77°C (rough estimate)
• 密度：
  1.0655 (rough estimate)
• 闪点：
  2℃
• 溶解度：
  氯仿（少量溶解）、乙醇（少量，超声处理）、甲醇（少量溶解）

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S24/25,S36
• 危险类别码：
  R40
• WGK Germany：
  2,3
• 海关编码：
  29372900
• 危险品运输编号：
  UN 1648 3 / PGII

制备方法与用途

用途
用作甾体激素药中间体，是睾酮和具有雄激素活性代谢产物的前体。有研究表明，这可能增加前列腺癌或胰腺癌的风险。

生产方法
本品并非天然产物，而是合成雄性激素的基础物质。可通过将雄烷-3,17-二酮、雄烷-3,17-二醇等化合物进行化学反应制得。

类别：有毒物品

可燃性危险特性：可燃；燃烧时会产生刺激性的烟雾。

储运特性：需存放在通风良好、低温干燥的库房中。

灭火剂：干粉、泡沫、砂土、二氧化碳或雾状水。

反应信息

• 作为反应物：
  描述：

  dl-Δ⁴-androstene-3,17-dione 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 甲酸 、 cerium(III) chloride heptahydrate 、 硫酸 、 双氧水 、 溶剂黄146 、 三乙胺 、 potassium hydroxide 、 锌 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 30.5h， 生成 (3β,4α,5β,8α,9β,10α,13α,14β)-4-methoxy-16-(phenylmethylene)androstane-3,17-diol diacetate
  参考文献：
  名称：

  Neurosteroid Analogues. 18. Structure–Activity Studies of ent-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone

  摘要：

  A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on gamma-aminobutyric acid type A (GABA(A)) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4 alpha-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids 0 occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA(A) receptor function.

  DOI：

  10.1021/jm401577c
• 作为产物：
  描述：

  1,3-Dimethyl-2-(7-methyl-trans,trans-3,7-tridecadien-11-ynyl)-2-cyclopentenol 在 甲醇 、 氢氧化钾 、 四氧化钌 、 四氯化锡 作用下， 生成 dl-Δ⁴-androstene-3,17-dione
  参考文献：
  名称：

  Formation of vinyl halides from vinyl cations generated by acetylenic participation in biomimetic polyene cyclizations

  摘要：

  DOI：

  10.1021/ja00391a017

文献信息

• NEUROACTIVE ENANTIOMERIC 15-, 16- AND 17-SUBSTITUTED STEROIDS AS MODULATORS FOR GABA TYPE-A RECEPTORS
  申请人：WASHINGTON UNIVERSITY

  公开号：US20150361125A1

  公开（公告）日：2015-12-17

  The present disclosure is generally directed to neuroactive enantiomeric 15-, 16- and 17-substituted steroids with additional optional substituents at carbons 3, 4, 6, 7, 10 and 13, and pharmaceutically acceptable salts thereof, for use as, for example, modulators for GABA type-A receptors. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

  本公开涉及具有额外可选取代基团的碳3、4、6、7、10和13的15、16和17位旋光异构的神经活性取代类固醇及其药学上可接受的盐，例如，用作GABA-A受体调节剂。本公开进一步涉及包含这种化合物的制药组合物。
• Decarboxylative Oxidation of Carboxylic Acids Using Photocatalysis and Copper Catalysis
  作者：Zhankui Sun、Muhammad Kashif Zaman、Shah Nawaz Khan、Yuanyuan Cai

  DOI：10.1055/a-2102-7006

  日期：2023.10

  A decarboxylative oxidation of carboxylic acids was developed through visible-light-induced photocatalysis with molecular oxygen as a green oxidant and copper as a co-catalyst. This reaction worked smoothly on various type of acids, and could potentially be used in modifications of natural products. The high efficiency of this transformation was demonstrated on over 40 substrates.

  通过可见光诱导光催化，以分子氧作为绿色氧化剂和铜作为助催化剂，开发了羧酸的脱羧氧化反应。该反应在各种类型的酸上都能顺利进行，并且有可能用于天然产物的修饰。这种转化的高效率在 40 多种底物上得到了证明。
• Neuroactive enantiomeric 15-, 16- and 17-substituted steroids as modulators for GABA type-A receptors
  申请人：Washington University

  公开号：US10202413B2

  公开（公告）日：2019-02-12

  The present disclosure is generally directed to neuroactive enantiomeric 15-, 16- and 17-substituted steroids with additional optional substituents at carbons 3, 4, 6, 7, 10 and 13, and pharmaceutically acceptable salts thereof, for use as, for example, modulators for GABA type-A receptors. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

  本公开内容一般涉及在碳3、4、6、7、10和13上具有额外任选取代基的神经活性对映体15、16和17-取代类固醇及其药学上可接受的盐，可用作例如GABA-A型受体的调节剂。本公开进一步涉及包含此类化合物的药物组合物。
• Propargylsilane function as a terminator of biomimetic polyene cyclizations leading to steroids
  作者：Rudolf Schmid、Peter L. Huesmann、William S. Johnson

  DOI：10.1021/ja00535a063

  日期：1980.7
• Neurosteroid Analogues. 17. Inverted Binding Orientations of Androsterone Enantiomers at the Steroid Potentiation Site on γ-Aminobutyric Acid Type A Receptors
  作者：Kathiresan Krishnan、Brad D. Manion、Amanda Taylor、John Bracamontes、Joseph H. Steinbach、David E. Reichert、Alex S. Evers、Charles F. Zorumski、Steven Mennerick、Douglas F. Covey

  DOI：10.1021/jm2014925

  日期：2012.2.9

  The enantiomer pair androsterone and ent-androsterone are positive allosteric modulators of gamma-aminobutyric acid (GABA) type A receptors. Each enantiomer was shown to bind at the same receptor site. Binding orientations of the enantiomers at this site were deduced using enantiomer pairs containing OBn substituents at either C-7 or C-11. 11 beta-OBn-substituted steroids and 7 alpha-OBn-substituted ent-steroids potently displace [S-35]-tert-butylbicyclophosphorothionate, augment GABA currents, and anesthetize tadpoles. In contrast, 7 beta-OBn-substituted steroids and 11 alpha-OBn-substituted ent-steroids have diminished actions. The results suggest that the binding orientations of the active analogues are inverted relative to each other with the 7 alpha- and 11 beta-substituents similarly located on the edges of the molecules not in contact with the receptor surface. Analogue potentiation of the GABA current was abrogated by an alpha(1) subunit Q241L mutation, indicating that the active analogues act at the same sites in alpha(1)beta(2)gamma(2L) receptors previously associated with positive neurosteroid modulation.