5α-Pregn-3-en-20-on | 4947-29-9

• 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: 5α-Pregn-3-en-20-on
• 英文别名: 1-[(5S,8R,9S,10S,13S,14S,17S)-10,13-dimethyl-2,5,6,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
• CAS: 4947-29-9
• 化学式: C₂₁H₃₂O
• 分子量: 300.484
• InChiKey: AMNWULQVHOJWMK-QYYVTAPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5α-Pregn-3-en-20-on 在 palladium on activated charcoal 吡啶 、 aluminum oxide 、 氢气 作用下， 以 四氯化碳 、 乙醚 为溶剂， 生成 20ξ-Methoxy-3α-trifluormethyl-5β-pregnan
  参考文献：
  名称：

  3-三氟甲基甾族化合物的合成。

  摘要：

  DOI：

  10.1021/jm00284a021
• 作为产物：
  描述：

  20β-Acetoxy-5α-pregn-3-en 生成 5α-Pregn-3-en-20-on
  参考文献：
  名称：

  Longevialle,P.; Goutarel,R., Bulletin de la Societe Chimique de France, 1965, p. 3225 - 3231

  摘要：

  DOI：

文献信息

• [EN] PROCESS FOR PREPARING HIGH PURITIY ALLOPREGNANOLONE AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ALLOPRÉGNANOLONE À HAUTE PURETÉ ET DE SES INTERMÉDIAIRES
  申请人：BIONICE S L U

  公开号：WO2020187965A1

  公开（公告）日：2020-09-24

  The invention relates to an efficient and industrially applicable process for the preparation and purification of allopregnanolone and intermediates thereof without the assistance of column chromatography.

  该发明涉及一种高效且工业适用的过程，用于制备和纯化羟孕酮和其中间体，无需使用柱层析法的辅助。
• Synthesis of novel pregnane-based 20-carboxamides via palladium-catalysed aminocarbonylation
  作者：Gábor Mikle、Alexandra Zugó、Erzsébet Szatnik、Anita Maxim、Sándor Mahó、László Kollár

  DOI：10.1007/s11696-020-01478-7

  日期：2021.5

  5α-pregn-20-ene-20-carboxamides were synthesized from the widely accessible 3β-acetoxy-pregn-5,16-dien-20-one (PDA) using selective hydrogenation, hydrazine and iodoalkene formation, as well as palladium-catalysed aminocarbonylation. The 20-iodo-20-ene derivatives, obtained from the corresponding 20-keto derivatives via their hydrazones, served as substrates. 23 new 20-carboxamides were obtained using various N-nucleophiles

  由广泛可得的3β-乙酰氧基-pregn-5,16-合成20-羧酰胺基孕烯衍生物，例如3β-乙酰氧基-5α-pregn-20-ene-20-羧酰胺和5α-pregn-20-ene-20-羧酰胺。 Dien-20-one（PDA）使用选择性加氢，肼和碘代烯烃的形成，以及钯催化的氨基羰基化。通过相应的20酮从相应的20-酮衍生物获得的20-碘-20-烯衍生物用作底物。使用各种氮素获得了23种新的20-羧酰胺-亲核试剂，范围从简单的伯胺到α-氨基酸酯。这种方法的新颖之处在于应用轻度，中度或高产率的反应来获得原本难以获得的具有药学重要性的甾族20-羧酰胺。换句话说，代替了例如甾醇或胆酸的酶促或合成降解，使用了基本骨架的功能化（“积累”方法）。
• Complex Metabolism of the Novel Neurosteroid, Ganaxolone, in Humans. A Unique Challenge for MIST Assessment
  作者：William L. Fitch、Steven Smith、Michael Saporito、Gregory Busse、Mingbao Zhang、Julie Ren、Michael E Fitzsimmons、Ping Yi、Stephen English、Adam Carter、Thomas A. Baillie

  DOI：10.1124/dmd.122.001218

  日期：——

  pharmacokinetics, metabolism, and excretion of [14C]-ganaxolone (GNX) were characterized in healthy male subjects (n = 8) following a single 300-mg (150 μCi) oral dose. GNX exhibited a short half-life of 4 hours in plasma, whereas total radioactivity had a half-life of 413 hours indicating extensive metabolism to long-lived metabolites. Identification of the major GNX circulating metabolites required extensive

  [ 14 C]-加奈索酮 (GNX)的人体药代动力学、代谢和排泄在健康男性受试者 ( n = 8)中进行了表征，单次口服剂量为 300 毫克 (150 μ Ci)。GNX 在血浆中表现出 4 小时的短半衰期，而总放射性的半衰期为 413 小时，表明广泛代谢为长寿命代谢物。主要 GNX 循环代谢物的鉴定需要液相色谱-串联质谱分析的广泛分离和纯化，以及体外研究、核磁共振光谱和合成化学支持。这表明 GNX 代谢的主要途径涉及 16 α的羟基化-羟基位置，20-酮的立体选择性还原得到相应的 20α-羟基甾醇，3α-羟基硫酸化。后一反应产生不稳定的叔硫酸盐，它消除了 H 2 SO 4的元素以在 A 环中引入双键。这些途径的组合，连同将 3 β-甲基取代基氧化成羧酸和在 20 α处硫酸化位置，导致血浆中的主要循环代谢物，称为 M2 和 M17。这些研究导致对不少于 59 种 GNX 代谢物的完整或部分
• PROCESS FOR PREPARING HIGH PURITIY ALLOPREGNANOLONE AND INTERMEDIATES THEREOF
  申请人：Bionice, S.L.U.

  公开号：EP3712161A1

  公开（公告）日：2020-09-23

  The invention relates to an efficient and industrially applicable process for the preparation and purification of allopregnanolone and intermediates thereof without the assistance of column chromatography. This is done by stereoinversion of the corresponding 3-beta.-OH compound to produce the corresponding 3.alpha.-carboxylic acid ester followed by work-up (precipitation from an organic solvent/water mixture and crystallisation from an apolar organic solvent), followed which may be followed by mild hydrolysis of the ester to produce the free 3.alpha-OH compound allopregnanolone. The post Mitsonobu work-up reduces the level of the 2(3)-ene elimination impurity I and the mild ester hydrolysis minimises the production of the 17.alpha.- epimeric impurity II.

  本发明涉及一种无需柱层析即可制备和纯化异孕甾醇酮及其中间体的高效工业适用工艺。制备方法是将相应的 3-beta.-OH 化合物进行立体转化，生成相应的 3.α.- 羧酸酯，然后进行精制（从有机溶剂/水混合物中沉淀，再从无极性有机溶剂中结晶），最后对酯进行温和水解，生成游离的 3.α-OH 化合物别孕烯醇酮。Mitsonobu 后加工可减少 2(3)- 烯消除杂质 I 的含量，而温和的酯水解可最大限度地减少 17.α.- 二元杂质 II 的产生。
• Neurosteroids: Can a 2alpha,3alpha-epoxy ring make up for the 3alpha-hydroxyl group?
  作者：Alexander Kasal、Miloš Buděšínský、Pavel Mareš、Zdena Krištofíková、Alcino J. Leitão、Maria Luisa Sá e Melo、Maria Manuel C. Silva

  DOI：10.1016/j.steroids.2015.11.007

  日期：2016.1

  Seven steroid epoxides were prepared from 5 alpha-pregn-2-en-20-one and 5 alpha-pregn-3-en-20-one and their side-chain derivatives. All compounds were tested in vitro for binding to gamma-aminobutyric acid (GABA(A)) receptor, some of them also in vivo for anticonvulsant action.2 alpha,3 alpha-Epoxy-5 alpha-pregnan-20-one inhibited the TBPS binding to the GABA(A) receptor and showed a moderate anticonvulsant action in immature rats. In contrast, its 3 alpha,4 alpha-isomer was inactive. More polar epoxide derivatives, modified at the side chain were less active or inactive.Noteworthy, diol 20, the product of trans-diaxial opening of the 2 alpha,3 alpha-epoxide 4, was not able to inhibit the TBPS binding, showing that the activity of the epoxide is due to the compound itself and not to its hydrolytic product.The 3 alpha-hydroxyl group is known to be essential for the GABA(A) receptor binding. Despite the shortness of in vivo effects which are probably due to metabolic inactivation of the products prepared, our results show that the 2 alpha,3 alpha-epoxy ring is another structural pattern with ability to bind the GABA(A)R. (C) 2015 Elsevier Inc. All rights reserved.