3β-Hydroxy-16α-[(methoxycarbonyl)methyl]-5α-pregnan-20-one | 251985-46-3

• 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-Hydroxy-16α-[(methoxycarbonyl)methyl]-5α-pregnan-20-one
• 英文别名: 3β-hydroxy-16α-methoxycarbonylmethyl-5α-pregnan-20-one；methyl 2-[(3S,5S,8R,9S,10S,13S,14S,16S,17S)-17-acetyl-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-16-yl]acetate
• CAS: 251985-46-3
• 化学式: C₂₄H₃₈O₄
• 分子量: 390.563
• InChiKey: WDZJCHMRZIDETF-XMYYILBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β-Hydroxy-16α-[(methoxycarbonyl)methyl]-5α-pregnan-20-one 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 48.0h， 生成 16α-Carboxymethyl-3α-hydroxy-5α-pregnan-20-one
  参考文献：
  名称：

  Epalons: Synthesis of New 16α-Carboxymethyl Derivatives

  摘要：

  这些标题化合物（16α-羧甲基-3α-羟基-5α-孕酮及其钠盐和三乙胺盐）是通过将20-氧代孕-5,16-二烯-3β-乙酸酯与二甲基丙二酸酯共轭加成并脱羧而制备的。通过三苯基膦存在下的二乙基偶氮二甲酰胺和甲酸的Mitsunobu酰化反应进行了碳C-3的构型反转。

  DOI：

  10.1135/cccc19991479
• 作为产物：
  描述：

  2-((3S,8S,9S,10R,13S,14S,16R,17S)-3-Acetoxy-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-16-yl)-malonic acid 在 Lindlar's catalyst 盐酸 、 氢氧化钾 、 氢气 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 20.0~200.0 ℃ 、2.67 kPa 条件下， 反应 28.08h， 生成 3β-Hydroxy-16α-[(methoxycarbonyl)methyl]-5α-pregnan-20-one
  参考文献：
  名称：

  Epalons: Synthesis of New 16α-Carboxymethyl Derivatives

  摘要：

  这些标题化合物（16α-羧甲基-3α-羟基-5α-孕酮及其钠盐和三乙胺盐）是通过将20-氧代孕-5,16-二烯-3β-乙酸酯与二甲基丙二酸酯共轭加成并脱羧而制备的。通过三苯基膦存在下的二乙基偶氮二甲酰胺和甲酸的Mitsunobu酰化反应进行了碳C-3的构型反转。

  DOI：

  10.1135/cccc19991479

文献信息

• 3α-Fluoro Analogues of "Allopregnanolone" and Their Binding to GABAA Receptors
  作者：Barbora Slavíková、Alexander Kasal、Hana Chodounská、Zdena Krištofíková

  DOI：10.1135/cccc20020030

  日期：——

  (Diethylamino)sulfur trifluoride (DAST) was used for the preparation of 3α-fluorides (e.g., 3α-fluoro-5α-pregnane-12,20-dione, 3α-fluoro-16α-[(methoxycarbonyl)methyl]-5α-pregnan-20-one, methyl 3α-fluoro-5α-androstane-17β-carboxylate, 3α-fluoro-5β-pregnan-20-one) from the corresponding 3β-alcohols and for the preparation of 3,3-difluorides from 3-ketones (e.g., 3,3-difluoro-5α-pregnan-20-one). Boron trifluoride etherate was used for the conversion of an epoxide into 3α-fluoro-2β-hydroxy-5α-pregnan-20-one. Thein vitrobinding of the 3α-fluorides and the corresponding 3α-alcohols to the GABA_Areceptor was established using [³H]muscimol and [³⁵S]-tert-butylbicyclo[2.2.2]phosphorothionate as ligands.

  (Diethylamino)sulfur trifluoride（DAST）被用于从相应的3β-醇制备3α-氟化物（例如，3α-氟-5α-孕酮-12,20-二酮，3α-氟-16α-[(甲氧羰基)甲基]-5α-孕酮-20-酮，甲基3α-氟-5α-雄烷-17β-羧酸酯，3α-氟-5β-孕酮-20-酮），并用于从3-酮制备3,3-二氟化物（例如，3,3-二氟-5α-孕酮-20-酮）。三氟化硼醚酯用于将环氧化物转化为3α-氟-2β-羟基-5α-孕酮-20-酮。使用[3H]肌肽酒石酸盐和[35S]-tert-丁基双环[2.2.2]磷酸酯作为配体，建立了3α-氟化物和相应的3α-醇对GABA_A受体的in vitro结合。
• Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) Derivatives with a Polar Chain in Position 16α: Synthesis and Activity
  作者：Barbora Slavíková、Zdena Krištofíková、Hana Chodounská、Miloš Buděšínský、Fernando J. Durán、Adriana S. Veleiro、Gerardo Burton、Alexander Kasal

  DOI：10.1021/jm801454a

  日期：2009.4.9

  The lipophilic nature of allopregnanolone prevents its user-friendly application in human medicine. On inspiration by previously prepared allopregnanolone with a 16 alpha-bound tetraethylammonium salt, an attempt was made to produce allopregnanolone analogues with polar groups introduced into position 16 alpha with the goal of increasing water solubility, brain accessibility, and potency of neuroactive steroids. The Michael addition to derivatives of pregn-16-en-20-one was the key reaction step. The link between the steroid skeleton and the new side chain was either a methylene group (when diethyl malonate was added) or an oxygen atom (when a hydroxy derivative was added). [S-35]TBPS displacement was used to evaluate the products. Several carbamates (but not their parent alcohols) displaced TBPS from the picrotoxin binding site on GABA(A) receptors. Although none of them was more potent than the above ammonium salt, which stimulated this study, their nonionic nature should not prevent their passage into the brain.