dihydrotestosterone-19-aldehyde | 1393446-31-5

• 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: dihydrotestosterone-19-aldehyde
• 英文别名: 17beta-Hydroxy-3-oxo-5alpha-androstan-19-al；(5S,8S,9S,10R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-10-carbaldehyde
• CAS: 1393446-31-5
• 化学式: C₁₉H₂₈O₃
• 分子量: 304.43
• InChiKey: AFTUEXSGQQDJKS-GLOHGQAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  dihydrotestosterone-19-aldehyde 、 氧气 、 1-Deoxy-1-(7,8-dimethyl-2,4-dioxidobenzo[g]pteridin-10(5H)-yl)-5-O-phosphonopentitol 生成 Δ^1,10-dehydro-19-nordihydrotestosterone 、 草氨酸 、 氢(+1)阳离子 、 水 、 FMN
  参考文献：
  名称：

  Oxidation of Dihydrotestosterone by Human Cytochromes P450 19A1 and 3A4

  摘要：

  Dihydrotestosterone is a more potent androgen than testosterone and plays an important role in endocrine function. We demonstrated that, like testosterone, dihydrotestosterone can be oxidized by human cytochrome P450 (P450) 19A1, the steroid aromatase. The products identified include the 19-hydroxy- and 19-oxo derivatives and the resulting Delta(1,10)-, Delta(5,10)-, and Delta(9,10)-dehydro 19-norsteroid products (loss of 19-methyl group). The overall catalytic efficiency of oxidation was similar to 10-fold higher than reported for 3 alpha-reduction by 3 alpha-hydroxysteroid dehydrogenase, the major enzyme known to deactivate dihydrotestosterone. These and other studies demonstrate the flexibility of P450 19A1 in removing the 1- and 2-hydrogens from 19-norsteroids, the 2-hydrogen from estrone, and (in this case) the 1-, 5 beta-, and 9 beta-hydrogens of dihydrotestosterone. Incubation of dihydrotestosterone with human liver microsomes and NADPH yielded the 18- and 19-hydroxy products plus the Delta(1,10)-dehydro 19-nor product identified in the P450 19A1 reaction. The 18- and 19-hydroxylation reactions were attributed to P450 3A4, and 18- and 19-hydroxydihydrotestosterone were identified in human plasma and urine samples. The change in the pucker of the A ring caused by reduction of the Delta(4,5) bond is remarkable in shifting the course of hydroxylation from the 6 beta-, 2 beta-, 1 beta-, and 15 beta-methylene carbons (testosterone) to the axial methyl groups (18, 19) in dihydrotestosterone and demonstrates the sensitivity of P450 3A4, even with its large active site, to small changes in substrate structure.

  DOI：

  10.1074/jbc.m112.390047
• 作为产物：
  描述：

  雄诺龙 在 rat NADPH-P₄₅₀ reductase 、 human cytochrome P₄₅₀ 19A₁ , steroid aromatase 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 甲醇 、 aq. phosphate buffer 为溶剂， 反应 0.33h， 生成 (8R,9S,13S,14S,17S)-17-羟基-13-甲基-2,4,6,7,8,9,11,12,14,15,16,17-十二氢-1H-环戊并[a]菲-3-酮 、 dihydrotestosterone-19-aldehyde 、 Δ^9,10-dehydro-19-nordihydrotestosterone 、 2-hydroxy-Δ^1,10-dehydro-19-nordihydrotestosterone 、 Δ^1,10-dehydro-19-nordihydrotestosterone
  参考文献：
  名称：

  Oxidation of Dihydrotestosterone by Human Cytochromes P450 19A1 and 3A4

  摘要：

  Dihydrotestosterone is a more potent androgen than testosterone and plays an important role in endocrine function. We demonstrated that, like testosterone, dihydrotestosterone can be oxidized by human cytochrome P450 (P450) 19A1, the steroid aromatase. The products identified include the 19-hydroxy- and 19-oxo derivatives and the resulting Delta(1,10)-, Delta(5,10)-, and Delta(9,10)-dehydro 19-norsteroid products (loss of 19-methyl group). The overall catalytic efficiency of oxidation was similar to 10-fold higher than reported for 3 alpha-reduction by 3 alpha-hydroxysteroid dehydrogenase, the major enzyme known to deactivate dihydrotestosterone. These and other studies demonstrate the flexibility of P450 19A1 in removing the 1- and 2-hydrogens from 19-norsteroids, the 2-hydrogen from estrone, and (in this case) the 1-, 5 beta-, and 9 beta-hydrogens of dihydrotestosterone. Incubation of dihydrotestosterone with human liver microsomes and NADPH yielded the 18- and 19-hydroxy products plus the Delta(1,10)-dehydro 19-nor product identified in the P450 19A1 reaction. The 18- and 19-hydroxylation reactions were attributed to P450 3A4, and 18- and 19-hydroxydihydrotestosterone were identified in human plasma and urine samples. The change in the pucker of the A ring caused by reduction of the Delta(4,5) bond is remarkable in shifting the course of hydroxylation from the 6 beta-, 2 beta-, 1 beta-, and 15 beta-methylene carbons (testosterone) to the axial methyl groups (18, 19) in dihydrotestosterone and demonstrates the sensitivity of P450 3A4, even with its large active site, to small changes in substrate structure.

  DOI：

  10.1074/jbc.m112.390047

文献信息

• Oxidation of Dihydrotestosterone by Human Cytochromes P450 19A1 and 3A4
  作者：Qian Cheng、Christal D. Sohl、Francis K. Yoshimoto、F.Peter Guengerich

  DOI：10.1074/jbc.m112.390047

  日期：2012.8

  Dihydrotestosterone is a more potent androgen than testosterone and plays an important role in endocrine function. We demonstrated that, like testosterone, dihydrotestosterone can be oxidized by human cytochrome P450 (P450) 19A1, the steroid aromatase. The products identified include the 19-hydroxy- and 19-oxo derivatives and the resulting Delta(1,10)-, Delta(5,10)-, and Delta(9,10)-dehydro 19-norsteroid products (loss of 19-methyl group). The overall catalytic efficiency of oxidation was similar to 10-fold higher than reported for 3 alpha-reduction by 3 alpha-hydroxysteroid dehydrogenase, the major enzyme known to deactivate dihydrotestosterone. These and other studies demonstrate the flexibility of P450 19A1 in removing the 1- and 2-hydrogens from 19-norsteroids, the 2-hydrogen from estrone, and (in this case) the 1-, 5 beta-, and 9 beta-hydrogens of dihydrotestosterone. Incubation of dihydrotestosterone with human liver microsomes and NADPH yielded the 18- and 19-hydroxy products plus the Delta(1,10)-dehydro 19-nor product identified in the P450 19A1 reaction. The 18- and 19-hydroxylation reactions were attributed to P450 3A4, and 18- and 19-hydroxydihydrotestosterone were identified in human plasma and urine samples. The change in the pucker of the A ring caused by reduction of the Delta(4,5) bond is remarkable in shifting the course of hydroxylation from the 6 beta-, 2 beta-, 1 beta-, and 15 beta-methylene carbons (testosterone) to the axial methyl groups (18, 19) in dihydrotestosterone and demonstrates the sensitivity of P450 3A4, even with its large active site, to small changes in substrate structure.