4,4-二甲基胆甾-8,14-二烯-3-醇 | 19456-83-8

• 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
• 中文名称: 4,4-二甲基胆甾-8,14-二烯-3-醇
• 英文名称: MAS-412
• 英文别名: 4,4-dimethyl-5α-cholesta-8,14-dien-3β-ol；4,4-dimethyl-5α-cholest-8,14-diene-3β-ol；4,4-Dimethyl-5alpha-cholesta-8,14-dien-3beta-ol；(3S,5R,10S,13R,17R)-4,4,10,13-tetramethyl-17-[(2R)-6-methylheptan-2-yl]-1,2,3,5,6,7,11,12,16,17-decahydrocyclopenta[a]phenanthren-3-ol
• CAS: 19456-83-8
• 化学式: C₂₉H₄₈O
• 分子量: 412.7
• InChiKey: OGQJUYXFIOFTMA-PBJLWWPKSA-N

物化性质

• 沸点：
  510.1±49.0 °C(Predicted)
• 密度：
  0.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 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：

  4,4-二甲基胆甾-8,14-二烯-3-醇 生成 (3β,5α,20R)-4,4-dimethylcholesta-8,14-dien-3-ol benzoate
  参考文献：
  名称：

  Gautschi; Bloch, Journal of Biological Chemistry, 1958, vol. 233, p. 1343,1346

  摘要：

  DOI：
• 作为产物：
  描述：

  二氢羊毛固醇 反应 0.5h， 生成 4,4-二甲基胆甾-8,14-二烯-3-醇
  参考文献：
  名称：

  Metabolism of 32-hydroxylated 24,25-dihydrolanosterols by partially purified cytochrome P-45014DM from rat liver microsomes.

  摘要：

  在由大鼠肝脏部分纯化的细胞色素 P-450 组成的重组系统中，研究了 32- 羟基化的 24，25-二氢羊毛甾醇（1-3）的代谢，包括羊毛甾醇和 24，25-二氢羊毛甾醇（4，DHL）去甲基化的中间产物、和还原型烟酰胺腺嘌呤二核苷酸磷酸酯（NADPH）-细胞色素 P-450 还原酶组成的重组系统中进行了研究。重组系统将羊毛甾-8-烯-3β，32-二醇（1）转化为 4，4-二甲基-5α-胆甾烷-8，14，二烯-3β-醇（5），即 14-脱羟甲基化产物，转化方式与 4 相同。1 的细胞色素 P-45014DM 表观 Km 值约为 4 的 1/6。7-oxo-24, 25-dihydrolanosterol (6，7-oxo-DHL) 可抑制 4 的新陈代谢，后者是由羊毛甾醇或 4 合成胆固醇的有效抑制剂。不过，与 4 相比，6 对 1 的代谢抑制作用较弱。

  DOI：

  10.1248/cpb.36.3049

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。
• Steroid derivatives useful as hypocholesterolemics
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US05034548A1

  公开（公告）日：1991-07-23

  Lanosterols substituted in the 14 and/or 15 position(s) which are active in inhibiting lanosta-8,24-dien-3.beta.-ol 14.alpha.-methyl-demethylase activity, suppressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity, decreasing cholesterol synthesis and reducing serum cholesterol levels are disclosed.

  本发明涉及在14和/或15位置被替换的鲨烯醇，其在抑制鲨烯-8,24-二烯-3.beta.-醇14.alpha.-甲基-去甲基酶活性、抑制3-羟基-3-甲基谷氨酰辅酶A还原酶（HMGR）活性、降低胆固醇合成和减少血清胆固醇水平方面具有活性。
• Metabolism of 32-hydroxylated 24,25-dihydrolanosterols by partially purified cytochrome P-45014DM from rat liver microsomes.
  作者：YOSHIO SEKIGAWA、YOSHIKO SONODA、YOSHIHIRO SATO

  DOI：10.1248/cpb.36.3049

  日期：——

  Metabolism of 32-hydroxylated 24, 25-dihydrolanosterols (1-3), including the intermediate of lanosterol and 24, 25-dihydrolanosterol (4, DHL) demethylation, were studied in a reconstituted system consisting of rat liver partially purified cytochrome P-450, which catalyzes lanosterol 14-demethylation (cytochrome P-45014DM), and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase. The reconstituted system converted lanost-8-ene-3β, 32-diol (1) to 4, 4-dimethyl-5α-cholesta-8, 14, dien-3β-ol (5), the 14-dehydroxymethylated product, in the same way as 4. Lanost-7-ene-3β-32-diol (2) and lanost-6-ene-3β, 32-diol (3), the isomers of 1, were not converted to the corresponding 14-dehydroxymethylated products. The apparent Km value of cytochrome P-45014DM for 1 was about 1/6 of that for 4. The metabolism of 4 was inhibited by 7-oxo-24, 25-dihydrolanosterol (6, 7-oxo-DHL), which is a potent inhibitor of cholesterol biosynthesis from lanosterol or 4. However, the metabolism of 1 was less inhibited by 6 than that of 4.

  在由大鼠肝脏部分纯化的细胞色素 P-450 组成的重组系统中，研究了 32- 羟基化的 24，25-二氢羊毛甾醇（1-3）的代谢，包括羊毛甾醇和 24，25-二氢羊毛甾醇（4，DHL）去甲基化的中间产物、和还原型烟酰胺腺嘌呤二核苷酸磷酸酯（NADPH）-细胞色素 P-450 还原酶组成的重组系统中进行了研究。重组系统将羊毛甾-8-烯-3β，32-二醇（1）转化为 4，4-二甲基-5α-胆甾烷-8，14，二烯-3β-醇（5），即 14-脱羟甲基化产物，转化方式与 4 相同。1 的细胞色素 P-45014DM 表观 Km 值约为 4 的 1/6。7-oxo-24, 25-dihydrolanosterol (6，7-oxo-DHL) 可抑制 4 的新陈代谢，后者是由羊毛甾醇或 4 合成胆固醇的有效抑制剂。不过，与 4 相比，6 对 1 的代谢抑制作用较弱。
• A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway
  作者：Alexander Mazein、Steven Watterson、Wei-Yuan Hsieh、William J. Griffiths、Peter Ghazal

  DOI：10.1016/j.bcp.2013.03.021

  日期：2013.7

  that describes the cholesterol biosynthesis pathway (the mevalonate, the Kandutch-Russell and the Bloch pathway) and shunt pathway that leads to 24(S),25-epoxycholesterol synthesis. The diagram has been produced using the Systems Biology Graphical Notation (SBGN) and is available in the SBGN-ML format, a human readable and machine semantically parsable open community file format.

  胆固醇生物合成是健康和疾病中众多生物过程的中心代谢中心。现有文献中缺乏对胆固醇通路如何构建以及它如何与其他通路系统相互作用的详细、综合的单一视图描述。在这里，我们对现有文献进行了系统回顾，并提供了详细的途径图，描述了胆固醇生物合成途径（甲羟戊酸、Kandutch-Russell 和 Bloch 途径）和导致 24(S),25-环氧胆固醇合成的分流途径. 该图是使用系统生物学图形符号 (SBGN) 生成的，并以 SBGN-ML 格式提供，这是一种人类可读且机器语义可解析的开放社区文件格式。
• Purification and Characterization of Rat Sterol 14-Demethylase P450 (CYP51) Expressed in Escherichia coli
  作者：Y. Nitahara、Y. Aoyama、T. Horiuchi、M. Noshiro、Y. Yoshida

  DOI：10.1093/oxfordjournals.jbchem.a022536

  日期：1999.11.1

  Sterol 14-demethylase P460 (CYP51) is an essential enzyme for sterol biosynthesis by eukaryotes. We have cloned rat and human CYP51 cDNAs [Aoyama, Y., Noshiro, M., Gotoh, 0., Imaoka, S., Funae, Y., Kurosawa, N., Horiuchi, T, and Yoshida, Y. (1996) J. Biochenu 119, 926–933]. The cloned rat CYP51 cDNA was expressed in Escherichia coli with modification of the N-terminal amino acid sequence, and the expressed protein (CYP51m) was purified to gel-electrophoretic homogenity. The spectrophotometrically determined specific content of CYP51m was 16 nmol/mg protein and the apparent molecular weight was estimated to be 53, 000 on SDS-PAGE. Soret peaks of the oxidized and reduced CO-complex of CYP51m were observed at 417 and 447 mn, respectively. The purified CYP51m catalyzed the 14-demethylation of lanosterol and 24, 25-dihydrolanosterol upon reconstitution with NADPH-P450 reductase purified from rat liver microsomes. The apparent Km and Vmnx values for lanosterol were 10.5 μM and 13.9 nmol/min/nmol P450, respectively, and those for 24, 25-dihydrolanosterol were 20.0 jjM and 20.0 nmol/min/nmol P450, respectively. The lanosterol demethylase activity of the reconstituted system of CYP51m was inhibited by ketoconazole, itraconazole and fluconazole with apparent IC50 values of 0.2, 0.7, and 160 respectively.

  固醇14-脱甲基酶P460（CYP51）是生物体固醇生物合成所必需的酶。我们已经克隆了大鼠和人类CYP51的cDNA [Aoyama, Y., Noshiro, M., Gotoh, 0., Imaoka, S., Funae, Y., Kurosawa, N., Horiuchi, T, and Yoshida, Y. (1996) J. Biochenu 119, 926–933]。克隆的大鼠CYP51的cDNA在大肠杆菌中表达，N端氨基酸序列经过修饰，表达的蛋白（CYP51m）纯化后凝胶电泳均匀。通过分光光度法测定的CYP51m的特异性含量为16 nmol/mg蛋白，SDS-PAGE上测得的表观分子量为53,000。CYP51m氧化和还原CO复合物的索雷峰分别在417和447 mn处观察到。纯化的CYP51m与从大鼠肝脏微粒体中纯化的NADPH-P450还原酶重组后，催化了羊毛甾醇和24,25-二氢羊毛甾醇的14-脱甲基化。羊毛甾醇的表观Km和Vmnx值