5α-androstan-11β-ol-3,17-dione | 599-11-1

• 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: 5α-androstan-11β-ol-3,17-dione
• 英文别名: 11β-Hydroxy-5α-androstan-3,17-dion；5α-Androstan-11β-ol-3,17-dion；11β-hydroxy-5α-androstane-3,17-dione；11β-hydroxyandrostanedione；11beta-Hydroxy-5alpha-Androstane-3,17-dione；(5S,8S,9S,10S,11S,13S,14S)-11-hydroxy-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 599-11-1
• 化学式: C₁₉H₂₈O₃
• 分子量: 304.43
• InChiKey: FZEAQJIXYCPBLD-NYNCOMEHSA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）
• 沸点：
  453.4±45.0 °C(Predicted)
• 密度：
  1.152±0.06 g/cm3(Predicted)
• 熔点：
  226-227 °C(Solv: ethyl ether (60-29-7))

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5α-androstan-11β-ol-3,17-dione 在 Beauveria bassiana KCH 1065 作用下， 以 丙酮 为溶剂， 反应 96.0h， 以9.38%的产率得到11beta-羟基睾酮
  参考文献：
  名称：

  Microbial Baeyer–Villiger oxidation of 5α-steroids using Beauveria bassiana. A stereochemical requirement for the 11α-hydroxylation and the lactonization pathway

  摘要：

  Beauveria bassiana KCH 1065, as was recently demonstrated, is unusual amongst fungal biocatalysts in that it converts C-19 3-oxo-4-ene and 3 beta-hydroxy-5-ene as well as 3 beta-hydroxy-5 alpha-saturated steroids to 11 alpha-hydroxy ring-D lactones. The Baeyer-Villiger monooxygenase (BVMO) of this strain is distinguished from other enzymes catalyzing BVO of steroidal ketones by the fact that it oxidizes solely substrates with 11 alpha-hydroxyl group. The current study using a series of 5 alpha-saturated steroids (androsterone, 3 alpha-androstanediol and androstanedione) has highlighted that a small change of the steroid structure can result in significant differences of the metabolic fate. It was found that the 3 alpha-stereochemistry of hydroxyl group restricted "normal" binding orientation of the substrate within 11 alpha-hydroxylase and, as a result, androsterone and 3 alpha-androstanediol were converted into a mixture of 7 beta-, 11 alpha- and 7 alpha-hydroxy derivatives. Hydroxylation of androstanedione occurred only at the 11 alpha-position, indicating that the 3-oxo group limits the alternative binding orientation of the substrate within the hydroxylase. Only androstanedione and 3 alpha-androstanediol were metabolized to hydroxylactones. The study uniquely demonstrated preference for oxidation of equatorial (11 alpha-, 7 beta-) hydroxyketones by BVMO from B. bassiana. The time course experiments suggested that the activity of 17 beta-HSD is a factor determining the amount of produced ring-D lactones. The obtained 11 alpha-hydroxylactones underwent further transformations (oxy-red reactions) at C-3. During conversion of androstanedione, a minor dehydrogenation pathway was observed with generation of 11 alpha,17 beta-dihydroxy-5 alpha-androst-1-en-3-one. The introduction of C1-C2 double bond has been recorded in B. bassiana for the first time. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2014.01.006
• 作为产物：
  描述：

  氢化可的松 在 potassium phosphate 、 氢气 、 4-甲基苯磺酸吡啶 、 Rh/C 、 三乙胺 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 乙酸乙酯 为溶剂， 反应 51.0h， 生成 5α-androstan-11β-ol-3,17-dione
  参考文献：
  名称：

  11β-羟基雄酮的公斤级合成

  摘要：

  本文介绍了从廉价且容易获得的氢化可的松 (1) 中大规模大规模合成酮类固醇结构单元 11β-羟基雄甾酮 (2)。还描述了最初的发现路线，该路线以克为单位进行，经过八个步骤实现了 3-6% 的产率。路线重新设计的关键是合并两个立体选择性步骤，设置所需的 5α-H 和 3α-OH 手性中心，并进行优化以最大程度地减少色谱纯化。然后，该工艺路线在公斤级进行，通过四个步骤实现了 21-28% 的产率。

  DOI：

  10.1021/acs.oprd.4c00084

文献信息

• [EN] OXYSTEROLS AND METHODS OF USE THEREOF<br/>[FR] OXYSTÉROLS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2018075698A1

  公开（公告）日：2018-04-26

  Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R1, R2, R3, R4, R5, R6, and RG are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

  根据公式(A)提供化合物：以及药用可接受的盐和药物组合物；其中R1、R2、R3、R4、R5、R6和RG如本文所述定义。本发明的化合物被认为对预防和治疗多种疾病有用。
• Zur Lokalisierung funktioneller Gruppen in Steroiden mit Hilfe der Massenspektrometrie, I Ketosteroide
  作者：Hugo Obermann、Margot Spiteller‐Friedmann、Gerhard Spiteller

  DOI：10.1002/cber.19701030521

  日期：1970.5

  Die Lokalisierung von Hydroxylgruppen am Steroidskelett gelingt in fast allen Fällen über eine Oxydation zu den entsprechenden Ketonen, da deren Massenspektren sehr charakteristisch sind. Sie erlauben meist auch Aussagen über die Verknüpfung des A/B-Ringsystems.

  在快速的AllenFällenübereine Oxydation zu Ste entsprechenden Ketonen中的Steroidskelett gelingt上的羟基化合物发生了反应。Sie erlauben可以用于A / B环系统。
• Substratspezifische Hydroxylierungen von Steroiden mittels Pilz-Stämmen der Gattung<i>Gibberella</i>. Mikrobiologische Reaktionen, 9. Mitteilung
  作者：J. Urech、E. Vischer、A. Wettstein

  DOI：10.1002/hlca.19600430417

  日期：——

  Continning our earlier work on the action of fungi of the genus Gibberella on steroids we have shown that G. saubinetti (MONT. SACC. has the ability of hydroxylating steroids in the 6β- or the 15α-position. On the other hand, the steroid transforming properties of G. baccata (WALLR. SACC. seem to be limited to 15α-hydroxylation. Some interesting substrate specificity has been observed in this connection

  继续我们对赤霉菌属真菌对类固醇的作用的早期研究，我们表明G. saubinetti（MONT。SACC。具有在6β-或15α-位羟基化类固醇的能力。另一方面，类固醇转化的性质G.山定子（WALLR。SACC。似乎仅限于15α羟基化。一些有趣的底物特异性已在这方面，已观察到。15α羟基Δ 4雄甾烯3，已对所得到的17二酮这些实验过程中的第一次。
• [EN] OXYSTEROLS AND METHODS OF USE THEREOF<br/>[FR] OXYSTÉROLS ET LEURS MÉTHODES D'UTILISATION
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2018009867A1

  公开（公告）日：2018-01-11

  Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R1, R2, R3, and R6, R11a, and R11b are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

  根据公式（I）提供化合物及其药用可接受盐和药物组合物；其中R1、R2、R3、R6、R11a和R11b如本文所定义。本发明的化合物被认为对预防和治疗各种疾病条件有用。
• Hydroxysteroid Dehydrogenase-Catalyzed Highly Regio-, Chemo-, and Enantioselective Hydrogenation of 3-Keto in Steroids
  作者：Chunling Zeng、Shitang Xu、Jie Shen、Saijie Zhao、Xinhua Xu、Lifen Peng

  DOI：10.1021/acs.orglett.3c03557

  日期：2024.1.12

  A highly selective hydrogenation of 3-keto in steroids to 3-hydroxyl steroids catalyzed by hydroxysteroid dehydrogenases (HSDHs) was demonstrated. The Ct3α-HSDH-catalyzed hydrogenation generated 3α-hydroxyl steroids as the main enantiopure isomers in high yields, while the Ss3β-HSDH catalytic system afforded 3β-hydroxyl steroids in excellent yields. In both catalytic systems, the hydrogenation proceeded

  证明了在羟基类固醇脱氢酶 (HSDH) 的催化下，类固醇中的 3-酮基可以高度选择性地氢化为 3-羟基类固醇。 Ct3α-HSDH催化的氢化反应以高产率产生了作为主要对映体纯异构体的3α-羟基类固醇，而Ss3β-HSDH催化体系则以优异的产率产生了3β-羟基类固醇。在两种催化体系中，氢化反应在 3-酮基上进行区域选择性，7-、11-、17-和 20-酮基几乎未反应，并且在 C=C 键和酯基未受攻击的情况下进行化学选择性氢化。我们的HSDH促进的氢化反应具有区域选择性、化学选择性和对映选择性高、收率好、条件温和、底物范围广、适合克级合成等优点。值得注意的是，通过我们的氢化方法，可以轻松、高产地获得脱氢表雄酮、布烯醇酮和阿法沙酮等生物活性分子。