3β,7β-Dihydroxy-5α-androstan-17-on | 25848-69-5

• 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: 3β,7β-Dihydroxy-5α-androstan-17-on
• 英文别名: 3β,7β-dihydroxy-5α-androstane-17-one；3beta-7beta-Dihydroxy-5alpha-androstane-17-one；7-beta-Hydroxyepiandrosterone；(3S,5R,7S,8R,9S,10S,13S,14S)-3,7-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one
• CAS: 25848-69-5
• 化学式: C₁₉H₃₀O₃
• 分子量: 306.445
• InChiKey: VFPMCLQMAUVEHD-UCPSWNCLSA-N

物化性质

• 熔点：
  241 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  454.7±45.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

制备方法与用途

7β-羟基-雄酮（7β-羟-EpiA）可与ERβ结合，具有抗炎和神经保护作用。它是一种内源性的雄激素衍生物，来源于脱氢表雄酮。

反应信息

• 作为反应物：
  描述：

  3β,7β-Dihydroxy-5α-androstan-17-on 在 chromium(VI) oxide 、 硫酸 作用下， 以52 mg的产率得到5α-androstane-1,7,17-trione
  参考文献：
  名称：

  微生物转化。第4部分。秀丽线虫Cunninghamella elegans对5α-雄激素17-和17a-氮杂-D-homo-5α-雄激素17-的微生物转化

  摘要：

  秀丽隐杆线虫对5α-雄甾烷17-one，3β-乙酰氧基和3α-羟基衍生物的微生物转化主要由1β，7-二羟基化或7-单羟基化。3α-乙酰氧基-5α-雄烷-17-主要发生6β，11β-二羟基化。17a- Aza- D -homo-5α-androstan-17-one和3α-乙酰氧基衍生物在6β或7α处主要发生单羟基化反应，而3β-乙酰氧基衍生物虽然进行类似的单羟基化反应却得到良好的收率。 9α-单羟基化产物。

  DOI：

  10.1039/p19810001041
• 作为产物：
  描述：

  3β-acetoxy-7β-hydroxy-5α-androstane 在 水 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以94%的产率得到3β,7β-Dihydroxy-5α-androstan-17-on
  参考文献：
  名称：

  Synthesis of 7β-hydroxy-epiandrosterone

  摘要：

  The synthesis of 7 beta-hydroxy-epiandrosterone (6) possessing strong anti-inflammatory properties was achieved starting from 3 beta-acetoxy-17,17-(ethylenedioxy)-5-androsten (1). This approach involved as a main step an allylic oxidation of the C-7 followed by two reduction reactions of the double bond and of the carbonyl group. This stereoselective synthesis in 5 steps gave 7 beta-hydroxy-epiandrosterone in 63% overall yield. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.08.003

文献信息

• Hydroxylation of DHEA and its analogues by Absidia coerulea AM93. Can an inducible microbial hydroxylase catalyze 7α- and 7β-hydroxylation of 5-ene and 5α-dihydro C19-steroids?
  作者：Natalia Milecka-Tronina、Teresa Kołek、Alina Świzdor、Anna Panek

  DOI：10.1016/j.bmc.2013.11.050

  日期：2014.1

  coerulea AM93. DHEA and androstenediol were transformed to the mixture of allyl 7-hydroxy derivatives, while EpiA and 5α-androstan-3,17-dione were converted mainly to 7α- and 7β-alcohols accompanied by 9α- and 11α-hydroxy derivatives. On the basis of (i) time course analysis of hydroxylation of the abovementioned substrates, (ii) biotransformation with resting cells at different pH, (iii) enzyme inhibition

  在本文中，我们着重研究了Absidia coerulea AM93对DHEA，雄烯二醇，表雄甾酮和5α-雄烷-3,17-二酮进行7-羟基化的过程。除此之外，我们提出了对蓝藻中类固醇的羟基化的初步分析。AM93。DHEA和雄烯二醇被转化为烯丙基7-羟基衍生物的混合物，而EpiA和5α-雄烷-3,17-二酮主要转化为7α-和7β-醇，并伴有9α-和11α-羟基衍生物。基于（i）上述底物羟基化的时程分析，（ii）在不同pH下静息细胞的生物转化，（iii）酶抑制分析以及（iv）底物C–H键之间的几何关系经历羟基化和辅因子结合的活性氧原子，但假定相同的酶可催化氧化ç 7 -H α以及为C 7 -H β在-5-烯和5α二氢C键19-类固醇。在底物的结构和羟基化的区域选择性之间观察到的相关性表明，正常的结合酶-底物复合物中可能发生7β-羟基化，而在反向反向结合复合物中则发生7α-羟基化。
• Microbial Transformation of Epiandrosterone by Aspergillus Sydowii
  作者：Kudret Yildirim、Ali Kuru

  DOI：10.3184/174751916x14786062524888

  日期：2016.12

  Incubation of epiandrosterone with Aspergillus sydowii MRC 200653 afforded ten metabolites. The fungal dehydrogenation of epiandrosterone is reported for the first time. The formation of the major metabolite, 6β-hydroxyandrost-4-ene-3,17-dione, involved first dehydrogenation to give a 4-ene and then hydroxylation at C-6β. Small amounts of the substrate were hydroxylated at C-1α, C-7α, C-7β and C-11α

  表雄酮与 Aspergillus sydowii MRC 200653 一起孵育得到 10 种代谢物。表雄酮的真菌脱氢是首次报道。主要代谢物 6β-hydroxyandrost-4-ene-3,17-dione 的形成涉及首先脱氢生成 4-ene，然后在 C-6β 处羟基化。少量底物在 C-1α、C-7α、C-7β 和 C-11α 处羟基化。
• Hexose-6-phosphate Dehydrogenase Modulates 11β-Hydroxysteroid Dehydrogenase Type 1-Dependent Metabolism of 7-keto- and 7β-hydroxy-neurosteroids
  作者：Lyubomir G. Nashev、Charlie Chandsawangbhuwana、Zoltan Balazs、Atanas G. Atanasov、Bernhard Dick、Felix J. Frey、Michael E. Baker、Alex Odermatt

  DOI：10.1371/journal.pone.0000561

  日期：——

  BackgroundThe role of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the regulation of energy metabolism and immune system by locally reactivating glucocorticoids has been extensively studied. Experiments determining initial rates of enzyme activity revealed that 11β-HSD1 can catalyze both the reductase and the dehydrogenase reaction in cell lysates, whereas it predominantly catalyzes the reduction of cortisone to cortisol in intact cells that also express hexose-6-phosphate dehydrogenase (H6PDH), which provides cofactor NADPH. Besides its role in glucocorticoid metabolism, there is evidence that 11β-HSD1 is involved in the metabolism of 7-keto- and 7-hydroxy-steroids; however the impact of H6PDH on this alternative function of 11β-HSD1 has not been assessed.MethodologyWe investigated the 11β-HSD1-dependent metabolism of the neurosteroids 7-keto-, 7α-hydroxy- and 7β-hydroxy-dehydroepiandrosterone (DHEA) and 7-keto- and 7β-hydroxy-pregnenolone, respectively, in the absence or presence of H6PDH in intact cells. 3D-structural modeling was applied to study the binding of ligands in 11β-HSD1.Principal FindingsWe demonstrated that 11β-HSD1 functions in a reversible way and efficiently catalyzed the interconversion of these 7-keto- and 7-hydroxy-neurosteroids in intact cells. In the presence of H6PDH, 11β-HSD1 predominantly converted 7-keto-DHEA and 7-ketopregnenolone into their corresponding 7β-hydroxy metabolites, indicating a role for H6PDH and 11β-HSD1 in the local generation of 7β-hydroxy-neurosteroids. 3D-structural modeling offered an explanation for the preferred formation of 7β-hydroxy-neurosteroids.ConclusionsOur results from experiments determining the steady state concentrations of glucocorticoids or 7-oxygenated neurosteroids suggested that the equilibrium between cortisone and cortisol and between 7-keto- and 7-hydroxy-neurosteroids is regulated by 11β-HSD1 and greatly depends on the coexpression with H6PDH. Thus, the impact of H6PDH on 11β-HSD1 activity has to be considered for understanding both glucocorticoid and neurosteroid action in different tissues.

  -hydroxy-neurosteroids。
• Combinations comprising MABA compounds and corticosteroids
  申请人：ALMIRALL, S.A.

  公开号：US10456390B2

  公开（公告）日：2019-10-29

  A combination which comprises (a) corticosteroid and (b) a dual muscarinic antagonist-β2 adrenergic agonist compound, or any pharmaceutically acceptable salt or solvate thereof.

  由(a)皮质类固醇和(b)双重毒蕈碱拮抗剂-β2 肾上腺素能激动剂化合物或其任何药学上可接受的盐或溶液组成的组合物。
• Immune modulation method using steroid compounds
  申请人：——

  公开号：US20030060425A1

  公开（公告）日：2003-03-27

  The invention provides compositions comprising formula 1 steroids, e.g., 16&agr;-bromo-3 &bgr;-hydroxy-5&agr;-androstan-17-one hemihydrate and one or more excipients, including compositions that comprise a liquid formulation comprising less than about 3% v/v water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using the compounds. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

  本发明提供了由式 1 类固醇（如 16&agr;-溴-3&bgr;-羟基-5&agr;-雄甾烷-17-酮半水合物）和一种或多种赋形剂组成的组合物，包括由含水量小于约 3% v/v 的液体制剂组成的组合物。这些组合物可用于制造改进的药物制剂。本发明还提供了类固醇化合物（如 16&agr;-溴-3&bgr;-羟基-5&agr;-雄甾烷-17-酮的类似物）的间歇给药方法和用于此类给药方案的组合物。本发明进一步提供了抑制病原体复制、改善与免疫失调相关的症状以及使用化合物调节受试者免疫反应的组合物和方法。本发明还提供了制造和使用这些免疫调节组合物和制剂的方法。