本胆烷-17β-醇-3-酮 | 571-22-2

• 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: 本胆烷-17β-醇-3-酮
• 中文别名: 5Β-雄甾烷-17Β-醇-3-酮
• 英文名称: 5β-androstan-17β-ol-3-one
• 英文别名: 5β-dihydrotestosterone；5beta-Dihydrotestosterone；17β-hydroxy-5β-androstan-3-one；17β-Hydroxy-5β-androstanon-(3)；5β-DHT；DHT；(5R,8R,9S,10S,13S,14S,17S)-17-hydroxy-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one
• CAS: 571-22-2
• 化学式: C₁₉H₃₀O₂
• 分子量: 290.446
• InChiKey: NVKAWKQGWWIWPM-MISPCMORSA-N

物化性质

• 熔点：
  143°C
• 沸点：
  372.52°C (rough estimate)
• 密度：
  1.0320 (rough estimate)
• 溶解度：
  氯仿（微溶）、乙醇（微溶）、甲醇（微溶）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险类别码：
  R20/21/22,R45,R46,R61
• RTECS号：
  BV8054000

反应信息

• 作为反应物：
  描述：

  本胆烷-17β-醇-3-酮 在 potassium tert-butylate 、 氧气 作用下， 以 叔丁醇 为溶剂， 反应 6.5h， 以16%的产率得到4-羟基-睾酮
  参考文献：
  名称：

  Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites

  摘要：

  4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated.Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandro-stenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry.Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3 beta-hydroxy-5 alpha-androstane-4,17-dione (2) and 3 alpha-hydroxy-5 beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3 xi,4 xi-dihydroxy,-5 xi-androstan-17-one (4, 6-11) except 3 alpha,4 alpha-dihydroxy-5 beta-androstan-17-one (5).Out of the 17 beta-hydroxylated analogs 4-hydroxytestosterone (18), 3 beta,17 beta-dihydroxy-alpha-androstan-4-one (19),3 alpha,17 beta-dihydroxy-5 beta-androstan-4-one (20), 5 alpha-androstane-3 beta,4 beta,17 beta-triol (21), 5 alpha-androstane-3 alpha,4 beta,17 beta-triol (26) and 5 alpha-androstane-3 alpha,4 alpha,17 beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2006.11.018
• 作为产物：
  描述：

  睾酮 在 recombinant human aldo-keto reductase 1D₁ 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 甲醇 为溶剂， 生成 本胆烷-17β-醇-3-酮
  参考文献：
  名称：

  AKR（醛酮还原酶）超家族的人酮类固醇还原酶对 5β 还原类固醇的立体特异性还原：AKR1C1-AKR1C4 通​​过 5β-还原酶途径在睾酮和孕酮代谢中的作用。

  摘要：

  睾酮和孕酮等活性性激素在肝脏中代谢为四氢类固醇以终止激素作用。一个主要的代谢途径，5β-途径，涉及 5β-类固醇还原酶（AKR1D1，其中 AKR 是指醛酮还原酶超家族），它催化 4-烯结构的还原，以及酮类固醇还原酶（AKR1C1-AKR1C4），催化 3-氧代基团的后续还原。四种人类 AKR1C 酶对 5β-二氢睾酮、5β-孕烷-3,20-二酮和 20α-羟基-5β-孕烷-3-one（中间 5β-二氢类固醇）对睾酮和孕酮代谢的 5β-途径的活性，进行了调查。液相色谱-MS 产品表征表明，三种类固醇的 3-氧代基团的还原主要有利于相应 3α-羟基类固醇的形成。立体化学通过分子对接来解释。这些酶的动力学特性将 AKR1C4 鉴定为负责睾酮 5β-四氢类固醇肝形成的主要酶，但表明人类 AKR1C 对孕酮 5β-四氢类固醇肝形成的不同途径和作用。AKR1C1-AKR1C4 催化反应的动力学与 AKR1D1

  DOI：

  10.1042/bj20101804

文献信息

• Chemoselective Hydrogenation of α,β-Unsaturated Carbonyls Catalyzed by Biomass-Derived Cobalt Nanoparticles in Water
  作者：Tao Song、Zhiming Ma、Yong Yang

  DOI：10.1002/cctc.201801987

  日期：2019.2.20

  selectivity for hydrogenation of C=C in α,β‐unsaturated carbonyls under mild conditions. A broad set of α,β‐aromatic and aliphatic unsaturated carbonyls were selectively reduced to their corresponding saturated carbonyls in up to 99 % yields with good tolerance of various functional groups. Meanwhile, a new straightforward one‐pot cascade synthesis of saturated carbonyls was realized with high activity and

  在本文中，我们报道了由竹笋中的生物质衍生的碳负载的钴纳米颗粒与水中的分子氢在水中将α，β-不饱和羰基高度化学选择性氢化为饱和羰基，这是使用非均相非贵金属催化剂的首个原型据我们所知进行这种有机转型。最佳钴纳米催化剂CoO x@ NC-800在温和条件下表现出显着的活性，对α，β-不饱和羰基中的C = C进行氢化。广泛的α，β-芳族和脂族不饱和羰基被选择性还原为相应的饱和羰基，收率高达99％，并且对各种官能团具有良好的耐受性。同时，通过酮与醛的交叉羟醛缩合，然后进行选择性加氢，实现了一种新的，直接的，高活性和高选择性的饱和羰基单锅级联反应。更重要的是，这种单罐策略适用于从容易获得的起始原料合成卢瑞瑞林A（一种多功能的生物活性和药用分子）的权宜之计，这进一步突出了该催化剂的实用性。此外，
• Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D2, and other endogenous and xenobiotic carbonyl compounds
  作者：Satoshi Endo、Toshiyuki Matsunaga、Atsuko Matsumoto、Yuki Arai、Satoshi Ohno、Ossama El-Kabbani、Kazuo Tajima、Yasuo Bunai、Shigeru Yamano、Akira Hara、Yukio Kitade

  DOI：10.1016/j.bcp.2013.08.024

  日期：2013.11

  for NADP(H) over NAD(H) at a physiological pH of 7.4. In the NADPH-linked reduction, 3HBD showed broad substrate specificity for a variety of quinones, ketones and aldehydes, including 3-, 17- and 20-ketosteroids and prostaglandin D(2), which were converted to 3alpha-, 17beta- and 20alpha-hydroxysteroids and 9alpha,11beta-prostaglandin F(2), respectively. Especially, alpha-diketones (such as isatin

  3-羟基己异巴比妥脱氢酶（3HBD）催化将NAD（P）（+）链接的3-羟基己异巴比妥氧化为3-羟基己异巴比妥。该酶被认为是异生物醇和某些羟基类固醇的脱氢酶，但其生理功能仍然未知。我们已经纯化了兔3HBD，分离了其cDNA，并检查了其对辅酶和底物的特异性，反应方向性和组织分布。3HBD是醛酮还原酶（AKR）超家族的成员（AKR1C29），并且在7.4的生理pH值下，NADP（H）优于NAD（H）。在与NADPH相关的还原反应中，3HBD对多种醌，酮和醛（包括3-，17-和20-酮类固醇和前列腺素D（2））显示出广泛的底物特异性，它们被转化为3alpha-，17beta-和20alpha -羟基类固醇和9alpha，11beta-前列腺素F（2），分别。特别是，α-二酮（如isatin和diacetyl）和脂质过氧化衍生的醛（如4-oxo-和4-hydroxy-2-nonenals）是显示低K（m）值（0
• Characterization of hamster NAD⁺-dependent 3(17)β-hydroxysteroid dehydrogenase belonging to the aldo-keto reductase 1C subfamily
  作者：Satoshi Endo、Misato Noda、Akira Ikari、Kenjiro Tatematsu、Ossama El-Kabbani、Akira Hara、Yukio Kitade、Toshiyuki Matsunaga

  DOI：10.1093/jb/mvv057

  日期：2015.11

  The cDNAs for morphine 6-dehydrogenase (AKR1C34) and its homologous aldo-keto reductase (AKR1C35) were cloned from golden hamster liver, and their enzymatic properties and tissue distribution were compared. AKR1C34 and AKR1C35 similarly oxidized various xenobiotic alicyclic alcohols using NAD+, but differed in their substrate specificity for hydroxysteroids and inhibitor sensitivity. While AKR1C34 showed 3α/17β/20α-hydroxysteroid dehydrogenase activities, AKR1C35 efficiently oxidized various 3β- and 17β-hydroxysteroids, including biologically active 3β-hydroxy-5α/β-dihydro-C19/C21-steroids, dehydroepiandrosterone and 17β-estradiol. AKR1C35 also differed from AKR1C34 in its high sensitivity to flavonoids, which inhibited competitively with respect to 17β-estradiol (Ki 0.11–0.69 μM). The mRNA for AKR1C35 was expressed liver-specific in male hamsters and ubiquitously in female hamsters, whereas the expression of the mRNA for AKR1C34 displayed opposite sexual dimorphism. Because AKR1C35 is the first 3(17)β-hydroxysteroid dehydrogenase in the AKR superfamily, we also investigated the molecular determinants for the 3β-hydroxysteroid dehydrogenase activity by replacement of Val54 and Cys310 in AKR1C35 with the corresponding residues in AKR1C34, Ala and Phe, respectively. The mutation of Val54Ala, but not Cys310Phe, significantly impaired this activity, suggesting that Val54 plays a critical role in recognition of the steroidal substrate.

  从金黄地鼠肝脏中克隆了羟基脱氢酶（AKR1C34）及其同源醛酮还原酶（AKR1C35）的 cDNA，并比较了它们的酶学性质和组织分布。AKR1C34 和 AKR1C35 均能利用 NAD+ 氧化各种外源性的脂环醇，但在羟基类固醇的底物特异性和抑制剂敏感性方面有所不同。AKR1C34 显示出 3α/17β/20α-羟基类固醇脱氢酶活性，而 AKR1C35 能有效氧化多种 3β-和 17β-羟基类固醇，包括具有生物活性的 3β-羟基-5α/β-二氢C19/C21-类固醇、脱氢表雄酮和 17β-雌二醇。AKR1C35 在黄酮类化合物的高敏感性方面也与 AKR1C34 不同，黄酮类化合物以竞争方式抑制 17β-雌二醇（Ki 0.11–0.69 μM）。AKR1C35 的 mRNA 在雄性地鼠中肝脏特异性表达，而在雌性地鼠中普遍表达，AKR1C34 的 mRNA 表达则显示出相反的性二态性。由于 AKR1C35 是 AKR 超家族中第一个 3(17)β-羟基类固醇脱氢酶，我们还通过将 AKR1C35 中的 Val54 和 Cys310 替换为 AKR1C34 中的相应残基 Ala 和 Phe，研究了 3β-羟基类固醇脱氢酶活性的分子决定因素。Val54Ala 突变显著损害了这一活性，而 Cys310Phe 突变则没有，这表明 Val54 在识别甾体底物中起着关键作用。
• AFFINITY ILLUDOFULVENE CONJUGATES
  申请人：AF Chemicals, LLC,

  公开号：US20210155583A1

  公开（公告）日：2021-05-27

  In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

  在该发明实施例中，用于治疗细胞群的组合物包括一种药物。该药物部分可以是伊卢多富烯类似物。在该发明实施例中，用于治疗细胞群的组合物包括亲和药物结合物（AMC）。亲和部分可以是抗体、抗体片段、受体蛋白、肽生长因子、抗血管生成蛋白、特异结合肽、蛋白酶可切割肽、糖肽、肽、肽毒素、蛋白毒素和寡核苷酸。亲和部分可以通过连接剂与药物共价结合。
• Conversion of Human Steroid 5β-Reductase (AKR1D1) into 3β-Hydroxysteroid Dehydrogenase by Single Point Mutation E120H
  作者：Mo Chen、Jason E. Drury、David W. Christianson、Trevor M. Penning

  DOI：10.1074/jbc.m111.338780

  日期：2012.5

  reductase 1D1 (AKR1D1) and AKR1C enzymes are essential for bile acid biosynthesis and steroid hormone metabolism. AKR1D1 catalyzes the 5beta-reduction of Delta(4)-3-ketosteroids, whereas AKR1C enzymes are hydroxysteroid dehydrogenases (HSDs). These enzymes share high sequence identity and catalyze 4-pro-(R)-hydride transfer from NADPH to an electrophilic carbon but differ in that one residue in the conserved

  人类醛酮还原酶 1D1 (AKR1D1) 和 AKR1C 酶对于胆汁酸生物合成和类固醇激素代谢至关重要。AKR1D1 催化 Delta(4)-3-酮类固醇的 5beta 还原，而 AKR1C 酶是羟基类固醇脱氢酶 (HSD)。这些酶具有高度的序列同一性并催化 4-pro-(R)-氢化物从 NADPH 转移到亲电子碳，但不同之处在于保守的 AKR 催化四分体 His(120)（AKR1D1 编号）中的一个残基被替换为AKR1D1 中的谷氨酸。我们发现 AKR1D1 E120H 突变体废除了 5beta 还原酶活性并引入了 HSD 活性。然而，E120H 突变体出人意料地偏爱具有 5alpha 配置的二氢类固醇，并且与大多数 AKR1C 酶不同，它显示出占主导​​地位的立体化学偏好，作为 3beta-HSD，而不是 3alpha-HSD。3beta-HSD 活性实现的催化效率高于迄今为止观察到的任何