5α-cholesta-8,14-dien-3β-ol | 19431-20-0

• 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-cholesta-8,14-dien-3β-ol
• 英文别名: 14-dehydrozymostenol；cholesta-8,14-dien-β-ol；5alpha-Cholesta-8,14-dien-3beta-ol；(3S,5S,10S,13R,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,11,12,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 19431-20-0
• 化学式: C₂₇H₄₄O
• 分子量: 384.646
• InChiKey: AWBZPJQUWZBRII-CXDHQSPESA-N

物化性质

• 熔点：
  116-117 °C(Solv: methanol (67-56-1))
• 沸点：
  498.6±44.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：3mg/mL，乙醇：2mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5α-cholesta-8,14-dien-3β-ol 在 aluminum isopropoxide 、 丁酮 作用下， 以34%的产率得到5α-cholestane-8,14-dien-3-one
  参考文献：
  名称：

  Synthesis of Meiosis-Activating Sterols Containing Fluorine.

  摘要：

  It is documented that specific types of sterol play a major role in the resumption of meiosis in oocytes from mice in vitro. 4,4-Dimethyl-5 alpha-cholesta-8,14,24-trien-3 beta-ol (FF-MAS) isolated from human follicular fluid and 4,4-dimethyl-5 alpha-cholesta-8,24-dien-3 beta-ol (T-MAS) isolated from bull testicular tissue, have been shown to activate (promote) meiosis in vitro. In order to evaluate the biological activity and stability of such compounds, new demethylsterol derivatives have been synthesised. Using diethylaminosulfur trifluoride (DAST) it was possible to synthesise selected Delta(8), Delta(14) sterols with mono and difluoro substitution at C3.

  DOI：

  10.3891/acta.chem.scand.52-0503
• 作为产物：
  描述：

  7-去氢胆固醇 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 5α-cholesta-8,14-dien-3β-ol
  参考文献：
  名称：

  胆酸5,7-dien-3β-ol向5α-cholesta-8,14-dien-3β-ol的酸催化双键迁移的立体和化学过程

  摘要：

  酸催化双键迁移 类固醇 5,7-二烯与5α-8,14-二烯 类固醇 化学，通过使用 cholesta-5,7-dien-3β-ol 参照图1，详细描述了该反应的立体和化学过程。治疗1的36％盐酸 在回流中 乙醇持续3小时，得到二烯醇的6∶11∶65∶16∶2混合物（93％）：5α-和5β-cholesta-6,8（14）-dien-3β- ols7a ，b，5α-和5β- cholesta-8,14-dien-3β-ols2a ，b和5α-胆甾醇14,16-dien-3β-ol 10a，以及烯酮（1.7％）：5β -胆甾-8（14） - ，5β -胆甾-14-和-14-外延-5β -胆甾-8-烯-3-酮11-13。使用实验7A，7B和图2a，2b所建议的反应顺序：1 → 7A，7B ⇆7,14-dienols 8A，8B ⇆图2a，2b ⇆8（14），15- dienols 9A，B ⇆ 10A，B，其中8a，

  DOI：

  10.1039/b001726o

文献信息

• Regulation of meiosis
  申请人：——

  公开号：US20030004148A1

  公开（公告）日：2003-01-02

  Compounds of Formula I and methods of regulating the meiosis in a mammalian germ cell which method comprises administering an effective amount of the compound of Formula I to a germ cell in need of such a treatment.

  公式I的化合物和调控哺乳动物生殖细胞减数分裂的方法，所述方法包括向需要此类治疗的生殖细胞中施用公式I的化合物的有效量。
• Structure of an integral membrane sterol reductase from Methylomicrobium alcaliphilum
  作者：Xiaochun Li、Rita Roberti、Günter Blobel

  DOI：10.1038/nature13797

  日期：2015.1

  Solving the X-ray crystal structure of a Δ14-sterol reductase and homologue of human C14SR and DHCR7, two enzymes that reduce specific carbon–carbon double bonds in the cholesterol biosynthetic pathway, may provide insight into how specific mutations in DHCR7 and lamin B receptor lead to human diseases. Sterols are found in animals, plants, fungi and some prokaryotes, where they serve a broad range of biological functions. The most abundant sterol in animals is cholesterol, which helps maintain the strength and permeability of the plasma membrane. Dozens of integral membrane enzymes are required for cholesterol synthesis and structures have been determined for only a few of them. Here Xiaochun Li et al. report the X-ray crystal structure of a Δ14-sterol reductase from the methanotrophic bacterium Methylomicrobium alcaliphilum at 2.7 Å resolution. This enzyme is a homologue of human C14SR and DHCR7, enzymes that reduce specific carbon–carbon double bonds in the cholesterol biosynthetic pathway. Its structure reveals two interconnected pockets, one cytoplasmic-facing and containing the NADPH-binding pocket, the other containing a lipid-bilayer-facing cavity that may contain the sterol-binding pocket. Analysis of this enzyme structure provide some insight into how specific mutations in DHCR7 and LBR lead to human diseases. Sterols are essential biological molecules in the majority of life forms. Sterol reductases1 including Δ14 -sterol reductase (C14SR, also known as TM7SF2), 7-dehydrocholesterol reductase (DHCR7) and 24-dehydrocholesterol reductase (DHCR24) reduce specific carbon–carbon double bonds of the sterol moiety using a reducing cofactor during sterol biosynthesis. Lamin B receptor2 (LBR), an integral inner nuclear membrane protein, also contains a functional C14SR domain. Here we report the crystal structure of a Δ14-sterol reductase (MaSR1) from the methanotrophic bacterium Methylomicrobium alcaliphilum 20Z (a homologue of human C14SR, LBR and DHCR7) with the cofactor NADPH. The enzyme contains ten transmembrane segments (TM1–10). Its catalytic domain comprises the carboxy-terminal half (containing TM6–10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer. Comparison with a soluble steroid 5β-reductase structure3 suggests that the reducing end of NADPH meets the sterol substrate at the juncture of the two pockets. A sterol reductase activity assay proves that MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate, demonstrating functional conservation to human C14SR. Therefore, our structure as a prototype of integral membrane sterol reductases provides molecular insight into mutations in DHCR7 and LBR for inborn human diseases.

  解析一个Δ14-甾醇还原酶的X射线晶体结构，以及它与人类C14SR和DHCR7的同源物（这两种酶在胆固醇生物合成途径中还原特定的碳–碳双键），可能会为了解DHCR7和层粘连蛋白B受体的特定突变如何导致人类疾病提供线索。甾醇在动物、植物、真菌和一些原核生物中普遍存在，发挥着广泛的生物功能。在动物中，胆固醇是最丰富的甾醇，它有助于维持细胞膜的强度和渗透性。胆固醇合成需要几十种整合膜酶，目前只有少数几种的结构已被确定。在这里，Xiaochun Li等人报告了一种来自甲烷营养细菌Methylomicrobium alcaliphilum的Δ14-甾醇还原酶的X射线晶体结构，分辨率为2.7 Å。这种酶是人类C14SR和DHCR7的同源物，后者在胆固醇生物合成途径中还原特定的碳–碳双键。其结构揭示了两个相互连接的口袋，一个朝向细胞质并包含NADPH结合口袋，另一个包含一个可能包含甾醇结合口袋的脂质双层面向腔体。对该酶结构的分析为理解DHCR7和LBR的特定突变如何导致人类疾病提供了一些线索。甾醇是大多数生命形式中必不可少的生物分子。甾醇还原酶包括Δ14-甾醇还原酶（C14SR，也称为TM7SF2）、7-脱氢胆固醇还原酶（DHCR7）和24-脱氢胆固醇还原酶（DHCR24），在甾醇生物合成中使用还原辅因子减少甾醇部分特定的碳–碳双键。层粘连蛋白B受体（LBR）是一个整合内核膜蛋白，也含有一个功能性C14SR结构域。在这里，我们报告了一种来自甲烷营养细菌Methylomicrobium alcaliphilum 20Z的Δ14-甾醇还原酶（MaSR1）的晶体结构，它与辅因子NADPH结合。该酶包含十个跨膜段（TM1–10）。其催化域由羧基末端一半（包含TM6–10）构成，并包围两个相互连接的口袋，其中一个面向细胞质并容纳NADPH，而另一个从脂质双层可及。与可溶性类固醇5β-还原酶结构的比较表明，NADPH还原末端在两个口袋的交界处与甾醇底物相接触。甾醇还原酶活性测定证明MaSR1可以还原胆固醇生物合成中间体的双键，显示出与人类C14SR的功能保守性。因此，我们的结构作为整合膜甾醇还原酶的原型提供了关于DHCR7和LBR突变与先天性人类疾病的分子见解。
• Steroid compounds, use of these compounds for the preparation of meiosis-regulating medicaments and method for the preparation of these compounds
  申请人：Schering AG

  公开号：US20020188143A1

  公开（公告）日：2002-12-12

  The present invention relates to steroid compounds of general formula X, which may advantageously be employed to stimulate meiosis in human oocytes, the steroid being specifically characterized by amino nitrogen bonded to C 17 of the steroid skeleton via a spacer A. 1

  本发明涉及通式X的类固醇化合物，这些化合物可优势地用于刺激人卵母细胞的减数分裂，该类固醇化合物的特征在于氨基氮通过间距A.1与类固醇骨架的C17键合。
• Aminosterol compounds, their use in the preparation of meiosis-regulating medicaments and method for their preparation
  申请人：Schering Aktiengesellschaft

  公开号：EP1245572A1

  公开（公告）日：2002-10-02

  The present invention relates to steroid compounds of general formula I, which may advantageously be employed to stimulate meiosis in human oocytes, the steroid being specifically characterized by amino nitrogen bonded to C17 of the steroid skeleton via a spacer A.

  本发明涉及通式I的类固醇化合物，这些化合物可优势地用于刺激人类卵母细胞的减数分裂，该类固醇化合物的特点是通过间隔物A与类固醇骨架的C17上的氨基氮键合。
• [EN] THIOMORPHOLINO STEROID COMPOUNDS, THE USE THEREOF FOR THE PREPARATION OF MEIOSIS-REGULATING MEDICAMENTS AND METHOD FOR THE PREPARATION THEREOF<br/>[FR] COMPOSES THIOMORPHOLINO STEROIDES, LEUR UTILISATION POUR LA PREPARATION DE MEDICAMENTS REGULANT LA MEIOSE ET PROCEDE DE PREPARATION ASSOCIE
  申请人：SCHERING AG

  公开号：WO2005014613A1

  公开（公告）日：2005-02-17

  The present invention relates to thiomorpholino steroid compounds of general formula (I), which may advantageously be employed to stimulate meiosis in human oocytes, the steroid being specifically characterized by a thiomorpholino moiety bonded to C17 of the steroid skeleton via an alkylen spacer.

  本发明涉及通式(I)的硫代吗啡诺类固醇化合物，其可优选地用于刺激人卵母细胞的减数分裂，该类固醇具有通过烷基间隔连接到类固醇骨架的C17的硫代吗啡诺基团的特征。