4-Pregnen-20,21-diol-3-one | 477977-81-4

• 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: 4-Pregnen-20,21-diol-3-one
• 英文别名: (8S,9S,10R,13S,14S,17S)-17-(1,2-dihydroxyethyl)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 477977-81-4
• 化学式: C₂₁H₃₂O₃
• 分子量: 332.483
• InChiKey: ZCFUAGVJMSGCHS-FYGMKCHKSA-N

物化性质

• 熔点：
  166-167 °C
• 沸点：
  507.8±23.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Pregnen-20,21-diol-3-one 、 nicotinamide adenine dinucleotide 生成 去氧皮质酮 、 氢(+1)阳离子 、 NADH
  参考文献：
  名称：

  大肠杆菌kduD编码一种氧化还原酶，可同时转化糖和类固醇底物。

  摘要：

  以前未鉴定的大肠杆菌氧化还原酶催化将真核甾体激素11-脱氧皮质酮（11-DOC）选择性还原为有价值的生物活性产物4-pregnen-20,21-diol-3-one。实际上，各种NAD（P）H依赖性氧化还原酶可催化C21类固醇的C-20羰基还原。但是，在大肠杆菌中从未描述过具有20-酮类固醇还原酶活性的酶。我们目前的研究旨在鉴定和表征对真核生物类固醇激素11-DOC具有20-酮类固醇还原酶活性的大肠杆菌酶。我们使用蛋白质色谱技术从大肠杆菌DH5α中部分纯化了该酶。质谱显示样品中存在三种NADH特异性氧化还原酶。克隆了编码这些氧化还原酶的基因，并在大肠杆菌UT5600（DE3）中过表达。仅由kduD基因编码的2-dehydro-3-deoxy-D-葡萄糖酸5-dehydrogenase（KduD）的过表达使11-DOC的全细胞生物转化成为可能。纯化的6xHis标记版本的KduD被纯化至均质，

  DOI：

  10.1007/s00253-014-5551-8
• 作为产物：
  描述：

  去氧皮质酮 在 17beta-estradiol 17-dehydrogenase 作用下， 生成 4-Pregnen-20,21-diol-3-one
  参考文献：
  名称：

  Structural requirements in 20-oxo-steroids for interaction with the catalytic site of 20.BETA.-hydroxysteroid dehydrogenase.

  摘要：

  进行了动力学测量，以研究20β-羟类固醇脱氢酶与一系列具有C-17和/或C-21羟基的类固醇之间的相互作用，并考虑了C-17和C-21附近区域对反应的20-氧基与酶催化位点相互作用的影响。将C-21的氢替换为羟基的17-脱氧类固醇衍生物导致表观Vmax值显著下降（降至约六分之一到九分之一），但表观Km值略微增加（约1.1到1.8倍）。在17-羟基类固醇衍生物的C-21处进行相同的改变对表观Vmax值几乎没有或没有造成下降，但表观Km值却增加（约1.4到1.8倍），这与17-脱氧类固醇衍生物的变化相似。在21-脱氧-11-脱氧类固醇衍生物中，17α-羟基取代体对表观Km值影响不大（约0.8到1.1倍），并导致表观Vmax值轻微下降（降至约三分之四到五分之二）。在21-脱氧-11-氧基类固醇衍生物中引入17α-羟基使表观Km值显著降低（降至约七分之一），而表观Vmax值中度下降（降至约五分之六到一半）。在21-羟基类固醇衍生物中引入17α-羟基使表观Vmax值增加约1.8到11倍，但对表观Km值几乎没有影响。这些结果表明，位于21或17α位点的羟基直接限制了20-氧基与酶催化位点之间的构象和取向，并影响了催化过程中的氢转移阶段。此外，在21和17α位点的取代基中，后者可能更优先影响20-氧基的反应效率。C-11的氧基的存在对21和17α位点取代基的影响具有间接作用。20-氧基在催化反应中的最佳取向可能发生在21-脱氧-17-脱氧-11-脱氧类固醇衍生物中。在一个理想的三元复合物中，类固醇的20-氧基可能朝向类固醇环的β面突出，且20-氧基与C-17的α-氢之间的构象几乎呈交错状态；而C-21与C-17的α-氢之间的角度在C-17至C-20轴上是倾斜的；20-氧基在空间上较远离C-13的β位甲基，更靠近C-16的β链。

  DOI：

  10.1248/cpb.28.730

文献信息

• Biocatalytic synthesis of 4-pregnen-20,21-diol-3-one, a selective inhibitor of human 5α-reductase type II
  作者：Frank Hannemann、Rita Bernhardt、Joachim Jose

  DOI：10.1080/14756360701425311

  日期：2007.1

  Biocatalysis, the conversion of substrates into valuable products by the use of enzymes, has some striking advantages in comparison to standard organic chemistry for drug synthesis. By biocatalysis, substrates that contain several identical reactive groups at different positions can be converted with high regio-selectivity and enantio-selectivity. In this study, an E. coli isolate (E132) was identified which was able to convert the steroid desoxycorticosterone into the product 4-pregnen-20,21-diol-3-one in real terms. The product was purified from the cell culture supernatant by HPLC and its structure was demonstrated by mass spectrometry and NMR spectroscopy. It was tested on inhibition of human 5 alpha-reductases type I and type II. At a concentration of 10 mu M, inhibition was 49.0% for type I and 81.8% for type II, whereas there was no inhibition of human aromatase (CYP19) at 20 mM and human 17 alpha-hydroxylase-C-17,C-20- lyase (CYP17) at 2.5 mu M detectable. The IC50 value of 4-pregnen-20,21-diol-3-one for human 5 alpha-reductase type II was determined to be 1.56 mu M.
• COMPOSITIONS FOR PROLIFERATION OF CELLS AND RELATED METHODS
  申请人：The Hospital For Sick Children

  公开号：EP2598150A2

  公开（公告）日：2013-06-05
• US8748177B2
  申请人：——

  公开号：US8748177B2

  公开（公告）日：2014-06-10
• [EN] COMPOSITIONS FOR PROLIFERATION OF CELLS AND RELATED METHODS<br/>[FR] COMPOSITIONS POUR LA PROLIFÉRATION DE CELLULES ET PROCÉDÉS ASSOCIÉS
  申请人：HOSPITAL FOR SICK CHILDREN

  公开号：WO2010039679A1

  公开（公告）日：2010-04-08

  We have discovered that p63 inhibition results in increased cellular proliferation. We have also performed a screen for agents capable of increasing cellular proliferation, (e.g., of stem cells such as skin-derived precursors (SKPs)). The invention therefore invention provides compositions, methods, and kits for increasing proliferation of cells, using compounds that decrease p63 expression or activity or using the compounds described herein. The invention also features methods of using these compounds for increasing hair growth, improving skin health, or promoting skin repair in a subject.
• Structural requirements in 20-oxo-steroids for interaction with the catalytic site of 20.BETA.-hydroxysteroid dehydrogenase.
  作者：TAKAO HAYAKAWA、TSUYOSHI TANIMOTO、JIRO KAWAMURA

  DOI：10.1248/cpb.28.730

  日期：——

  Kinetic measurements were made to investigate the interaction of 20β-hydroxysteroid dehydrogenase and a series of steroids with C-17 and/or C-21 hydroxyl groups, and the role of the region around C-17 and C-21 on the interaction of the reacting 20-oxo group with the catalytic site of the enzyme was considered. Substitution of a hydroxyl group for hydrogen at C-21 of 17-deoxy-steroid derivatives caused a significant decrease in the apparent Vmax value (to about one-sixth to one-ninth), but a slight increase in the apparent Km value (about 1.1- to 1.8-fold). The same change at C-21 of 17-hydroxy-steroid derivatives caused little or no decrease in the apparent Vmax value, but an increase in the apparent Km (about 1.4- to 1.8-fold) occurred which was similar to that with 17-deoxy-steroid derivatives. In 21-deoxy-11-deoxy-steroid derivatives, a 17α-hydroxyl substituent had little effect on the apparent Km value (about 0.8- to 1.1-fold) and produced a slight decrease in the apparent Vmax value (to about three-quarters to two-fifths). Introduction of a 17α-hydroxyl group into 21-deoxy-11-oxo-steroid derivatives led to a significant decrease in the apparent Km value (to about one-seventh) and a moderate decrease in the apparent Vmax value (to about five-sixths to one-half). Introduction of a 17α-hydroxyl group into 21-hydroxy-steroid derivatives caused the apparent Vmax value to increase by about 1.8- to 11-fold, but caused little or no decrease in the apparent Km value. These results suggest that the hydroxyl group at the 21- or 17α-position directly restricted the conformation and the orientation of the 20-oxo group towards the catalytic site of the enzyme and influenced the hydrogen transfer stage in the catalytic process, and also that, of the substituents at the 21- and 17α-positions, the latter may preferentially affect the reaction efficiency of the 20-oxo group. The presence of an oxo group at C-11 had an indirect influence on the effects of the substituents at the 21- and 17α-positions. The optimum orientation of the 20-oxo group for the catalytic reaction may occur in 21-deoxy-17-deoxy-11-deoxy-steroid derivatives. In an ideal ternary complex, the 20-oxo group of the steroid may project towards the β-face of the steroid ring and the conformation between the 20-oxo group and α-hydrogen of C-17 is nearly staggered, while that between C-21 and the α-hydrogen of C-17, looking along the C-17 to C-20 axis, is in a skew form ; the 20-oxo group is orientated rather far from the methyl group at the β-position of C-13 and more towards the β-chain of C-16.

  进行了动力学测量，以研究20β-羟类固醇脱氢酶与一系列具有C-17和/或C-21羟基的类固醇之间的相互作用，并考虑了C-17和C-21附近区域对反应的20-氧基与酶催化位点相互作用的影响。将C-21的氢替换为羟基的17-脱氧类固醇衍生物导致表观Vmax值显著下降（降至约六分之一到九分之一），但表观Km值略微增加（约1.1到1.8倍）。在17-羟基类固醇衍生物的C-21处进行相同的改变对表观Vmax值几乎没有或没有造成下降，但表观Km值却增加（约1.4到1.8倍），这与17-脱氧类固醇衍生物的变化相似。在21-脱氧-11-脱氧类固醇衍生物中，17α-羟基取代体对表观Km值影响不大（约0.8到1.1倍），并导致表观Vmax值轻微下降（降至约三分之四到五分之二）。在21-脱氧-11-氧基类固醇衍生物中引入17α-羟基使表观Km值显著降低（降至约七分之一），而表观Vmax值中度下降（降至约五分之六到一半）。在21-羟基类固醇衍生物中引入17α-羟基使表观Vmax值增加约1.8到11倍，但对表观Km值几乎没有影响。这些结果表明，位于21或17α位点的羟基直接限制了20-氧基与酶催化位点之间的构象和取向，并影响了催化过程中的氢转移阶段。此外，在21和17α位点的取代基中，后者可能更优先影响20-氧基的反应效率。C-11的氧基的存在对21和17α位点取代基的影响具有间接作用。20-氧基在催化反应中的最佳取向可能发生在21-脱氧-17-脱氧-11-脱氧类固醇衍生物中。在一个理想的三元复合物中，类固醇的20-氧基可能朝向类固醇环的β面突出，且20-氧基与C-17的α-氢之间的构象几乎呈交错状态；而C-21与C-17的α-氢之间的角度在C-17至C-20轴上是倾斜的；20-氧基在空间上较远离C-13的β位甲基，更靠近C-16的β链。