pregnenolone

• 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: pregnenolone
• 英文别名: 1-[(3S,8S,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
• 化学式: C₂₁H₃₂O₂
• 分子量: 316.484
• InChiKey: ORNBQBCIOKFOEO-ZRWJKECHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  pregnenolone 在 glucose-6-phosphate dehydrogenase 、 glucose 6-phosphate 、 recombinant bovine adenal cytochrome P₄₅₀ 17A₁ 、 recombinant bovine liver cytochrome P₄₅₀ reductase 、 还原型辅酶II(NADPH)四钠盐 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 生成 1-[(3S,8R,9S,10R,13S,14S)-3,17-dihydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl]ethanone
  参考文献：
  名称：

  A steroidogenic pathway for sulfonated steroids: The metabolism of pregnenolone sulfate

  摘要：

  In many tissues sulfonated steroids exceed the concentration of free steroids and recently they were also shown to fulfill important physiological functions. While it was previously demonstrated that cholesterol sulfate (CS) is converted by CYP11A1 to pregnenolone sulfate (PregS), further conversion of PregS has not been studied in detail. To investigate whether a steroidogenic pathway for sulfonated steroids exists similar to the one described for free steroids, we examined the interaction of PregS with CYP17A1 in a reconstituted in-vitro system. Difference spectroscopy revealed a K-d-value of 74.8 +/- 4.2 mu M for the CYP17A1-PregS complex, which is 2.5-fold higher compared to the CYP17A1-pregnenolone (Preg) complex. Mass spectrometry experiments proved for the first time that PregS is hydroxylated by CYP17A1 at position C17, identically to pregnenolone. A higher K-m- and a lower k(cat)-value for CYP17A1 using PregS compared with Preg were observed, indicating a 40% reduced catalytic efficiency when using the sulfonated steroid. Furthermore, we analyzed whether the presence of cytochrome b(5) (b(5)) has an influence on the CYP17A1 dependent conversion of PregS, as was demonstrated for Preg. Interestingly, with 17OH-PregS no scission of the 17,20-carbon-carbon bond occurs, when b(5) is added to the reconstituted in-vitro system, while b(5) promotes the formation of DHEA from 17OH-Preg. When using human SOAT-HEK293 cells expressing CYP17A1 and CPR, we could confirm that PregS is metabolized to 17OH-PregS, strengthening the potential physiological meaning of a pathway for sulfonated steroids. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.jsbmb.2014.07.005
• 作为产物：
  描述：

  3β-hydroxypregn-5-en-20-one-3-acetate 在 甲醇 、 potassium carbonate 作用下， 以92.81%的产率得到pregnenolone
  参考文献：
  名称：

  甾体类雄激素受体抑制剂、其制备方法及医药用途

  摘要：

  本发明涉及药物化学领域，具体涉及一系列甾体类雄激素受体抑制剂、其制备方法及医药用途，特别是用于治疗雄激素受体相关疾病的药物，如依赖于雄激素的细胞增殖，多毛症，痤疮，雄激素脱发等。本发明中涉及化合物的结构通式如下式，通式中各基团定义详见说明书。

  公开号：

  CN105601696A

文献信息

• Dehydration of alcohols catalyzed by copper(II) sulfate adsorbed on silica gel
  作者：Takeshi Nishiguchi、Nakahira Machida、Etsuko Yamamoto

  DOI：10.1016/s0040-4039(00)96565-1

  日期：1987.1

  Copper(II) sulfate adsorbed on silica gel efficiently dehydrated secondary and tertiary alcohols under mild conditions to give olefins. The rate of dehydration of tertiary alcohols is much faster than that of secondary alcohols.

  吸附在硅胶上的硫酸铜（II）在温和的条件下有效地使仲醇和叔醇脱水，得到烯烃。叔醇的脱水速率比仲醇的脱水速率快得多。
• Diversity‐Orientated Stereoselective Synthesis through Pd‐Catalyzed Switchable Decarboxylative C−N/C−S Bond Formation in Allylic Surrogates
  作者：Lei Deng、Arjan W. Kleij、Weibo Yang

  DOI：10.1002/chem.201805295

  日期：2018.12.20

  diversity‐orientated synthesis from easily available molecular synthons. Herein, an endogenous ligand‐controlled, Pd‐catalyzed allylic substitution allowing for either selective C−N or C−S bond formation using vinylethylene carbonates (VECs) and N‐sulfonylhydrazones as coupling partners has been developed. This versatile methodology provides a facile, divergent route for the highly chemo‐ and stereoselective

  反应物的可转换催化转化可能是从易于获得的分子合成子转向以多样性为导向的合成的强大方法。本文中，内源性配体控制的，Pd催化的烯丙基取代可使用碳酸乙烯基亚乙酯（VEC）和N选择性地形成CN或CS键已经开发了磺酰hydr作为偶联伙伴。这种通用的方法为功能性烯丙基砜或磺酰肼的高度化学和立体选择性合成提供了一条简便，多样化的途径。新开发的方案具有广泛的底物范围（将近80个实例），广泛的官能团耐受性和生物活性化合物后期功能化的潜力。对具有催化作用的π-烯丙基钯络合物的分离和晶体学分析表明，导致烯丙基产物的途径通过了先前提出的使用亲核试剂对VEC进行功能化的不同歧管。
• <i>p</i>-Toluenesulfonic Acid Adsorbed on Silica Gel: An Efficient Dehydrating Agent of Alcohols
  作者：Franco D'Onofrio、Arrigo Scettri

  DOI：10.1055/s-1985-31463

  日期：——

  Secondary and tertiary alcohols are efficiently dehydrated by reaction with p-toluenesulfonic acid supported on silica gel. In particular, the procedure allows the direct conversion of 3-hydroxy-steroids into Δ2-olefins or Δ3,5-dienes, without passing through the mesylate or tosylate esters.

  二级和三级醇通过与负载在硅胶上的对甲苯磺酸反应有效脱水。特别是，该方法允许将3-羟基类固醇直接转化为Δ2-烯烃或Δ3,5-二烯，而无需经过美克酸酯或对甲苯磺酸酯。
• α-Hydroxylation of ketones: Osmium tetroxide/N-methylmorpholine-N-oxide oxidation of silyl enol ethers
  作者：J.P. McCormick、Witold Tomasik、Mark W. Johnson

  DOI：10.1016/s0040-4039(01)92501-8

  日期：1981.1

  Osmium tetroxide/N-methylmorpholine-N-oxide oxidation of silyl enol ethers, derived from ketones with either kinetic or thermodynamic regiochemical control, produces α-ketols in good to excellent yields.

  甲硅烷基烯醇醚的四氧化s / N-甲基吗啉-N-氧化物氧化反应是通过动力学或热力学区域化学控制的方式从酮中衍生出来的，可产生高至优异收率的α-酮醇。
• CrO₃/NHPI Adsorbed on Activated Clay: A New Supported Reagent for Allylic Selective Oxidation of Δ⁵-Sterols
  作者：Jin Liu、Hong-You Zhu、Xiao-Hong Cheng

  DOI：10.1080/00397910802484114

  日期：2009.2.25

  Abstract Chromium trioxide and N-hydroxyphthalimide (NHPI) supported on activated clay could serve as an efficient and mild oxidant for allylic selective oxidation of Δ5-sterols. Thus, a ketone group could be easily introduced into the allylic position of Δ5-sterols with the existence of a sensitive 3β-hydroxyl group. The oxidant residue can be removed easily from the reaction mixture by filtration

  摘要 负载在活性粘土上的三氧化铬和 N-羟基邻苯二甲酰亚胺 (NHPI) 可以作为一种高效温和的氧化剂用于 Δ5-甾醇的烯丙基选择性氧化。因此，由于存在敏感的 3β-羟基，酮基可以很容易地引入 Δ5-甾醇的烯丙基位置。氧化剂残留物可以通过过滤轻松地从反应混合物中去除，并在 120°C 下重新活化 4-6 小时后重新使用。