11-Beta,17-alpha,21-三羟基-5-alpha-孕烯-3,20-二酮 | 516-41-6

• 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: 11-Beta,17-alpha,21-三羟基-5-alpha-孕烯-3,20-二酮
• 英文名称: 11β,17α,21-trihydroxy-5α-pregnane-3,20-dione
• 英文别名: 5-α-pregnane-11β,17α,21-triol-3,20-dione；11β,17,21-triol-5α-pregnane-3,20-dione；5α-pregnan-11β,17,21-triol-3,20-dione；5α-dihydrocortisol；11β,17,21-trihydroxy-5α-pregnane-3,20-dione；11β,17,21-Trihydroxy-5α-pregnan-3,20-dion；Hydrallostane；(5S,8S,9S,10S,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 516-41-6
• 化学式: C₂₁H₃₂O₅
• 分子量: 364.482
• InChiKey: ACSFOIGNUQUIGE-SERXDUEGSA-N

物化性质

• 熔点：
  234-240°
• 比旋光度：
  D25 +83° (acetone)
• 沸点：
  544.5±50.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（轻微，加热），甲醇（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.904
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11-Beta,17-alpha,21-三羟基-5-alpha-孕烯-3,20-二酮 在 吡啶 、 咪唑 、 氢氟酸 、 4-甲基苯磺酸吡啶 、 potassium tri-sec-butyl-borohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.33h， 生成 2-oxa-2-((3R,5S,8S,9S,10S,11S,13S,14S,17R)-3,11,17-trihydroxy-10,13-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethyl acetate
  参考文献：
  名称：

  Studies of steroids. Part CCL. Chemical conversion of corticosteroids to 3.ALPHA.,5.ALPHA.-tetrahydro derivatives. Synthesis of allotetrahydrocortisol glucuronides and allotetrahydrocortisone glucuronides.

  摘要：

  本文描述了异构四氢可的松（allo-THF）和异构四氢可的松（allo-THE）的 3-和 21-葡萄糖醛酸苷的合成。5α-Dihydrocortisol (5) 是通过选择性氢化 21-乙酰氧基-3，11β，17α-三羟基-3，5-孕二烯-20-酮 3-乙基醚 (3)，然后进行酸水解和皂化而制备的。在温和的条件下，5α-二氢可的松 21-四氢吡喃基醚（6）在四氢呋喃中用三仲丁基硼氢化钾处理时，C-3 处发生了区域选择性和立体选择性还原，得到了烯丙基-THF 21-四氢吡喃基醚（7）。该化合物被转化成关键中间体--烯丙基-THF 和烯丙基-THE 的 3-和 21-单乙酸酯。通过柯尼希斯-克诺尔（Koenigs-Knorr）反应，在 C-3 或 C-21 处引入葡萄糖醛酸残基。在皂化生成 3-葡萄糖醛酸（20、23）之前，C-17 处的碱敏感酮侧链作为 20-氨基脲受到保护。

  DOI：

  10.1248/cpb.38.1949
• 作为产物：
  描述：

  氢化可的松 以 乙醇 为溶剂， 反应 96.0h， 以62%的产率得到11-Beta,17-alpha,21-三羟基-5-alpha-孕烯-3,20-二酮
  参考文献：
  名称：

  Biotransformation of corticosteroids by Penicillium decumbens ATCC 10436

  摘要：

  The biotransformation of a series of corticosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the corresponding 5 alpha-dihydrosteroid was observed for all the Delta(4)-3-ketosteroids studied with the exception of deoxycorticosterone, which was converted to a Delta(1,4)-diene. Deoxycorticosterone acetate was, however, converted to a 5 alpha-dihydro product concomitant with ester hydrolysis. Other substrates carrying a C-21 acetoxy group were also hydrolyzed to the alcohol. In two cases (resulting from deoxycorticosterone acetate and 11-deoxycortisone) the 5 alpha-3-keto product was further reduced to the 3 beta-alcohol. No reduction of Delta(1,4)-dienes was observed.

  DOI：

  10.1016/0039-128x(95)00071-w

文献信息

• Direct organocatalytic stereoselective transfer hydrogenation of conjugated olefins of steroids
  作者：Dhevalapally B. Ramachary、Rajasekar Sakthidevi、P. Srinivasa Reddy

  DOI：10.1039/c3ra41519h

  日期：——

  catalyst 1b·D-CSA is mild enough to activate the various chiral cyclic enones through iminium ion formation during the organocatalytic transfer hydrogenations with Hantzsch ester 2a as a hydrogen source. Further, clear evidence for the selective formation of intermediate iminium species [I]+ have been characterized through on-line monitoring of controlled experiments by NMR and ESI-HRMS analyses.

  通过动力学控制和有机催化的顺-选择性转移氢化已成功地证明了各种类固醇的烯酮官能团的还原。在此，已经报道了通过有机催化的许多5β-类固醇的非对映选择性合成，其具有广泛的医学和药学应用。机理研究和产物的选择性清楚地表明，催化剂1b · D -CSA足够温和，可以在以汉茨sch酸酯2a为氢源的有机催化转移加氢过程中通过亚胺离子的形成来活化各种手性环状烯酮。此外，有明确的证据表明可以选择性地形成中间亚胺鎓类物质[ I] +通过NMR和ESI-HRMS分析对受控实验进行在线监测来表征。
• [EN] COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS<br/>[FR] COMPOSITIONS ET MÉTHODES POUR TRAITER DES TROUBLES DU SNC
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2016061527A1

  公开（公告）日：2016-04-21

  Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein (II), A, R1, R2, R3a, R4a, R4b, R5, R7a, and R7b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

  本文描述了式(I)的神经活性类固醇，或其药用可接受盐；其中(II)，A，R1，R2，R3a，R4a，R4b，R5，R7a和R7b如本文所定义。在某些实施例中，这些化合物被设想为GABA调节剂。本发明还提供了包括本发明化合物的药物组合物，以及使用和治疗方法，例如用于诱导镇静和/或麻醉。
• Potential Corticoid Metabolites: Chemical Synthesis of 3- and 21-Monosulfates and Their Double-Conjugates of Tetrahydrocorticosteroids in the 5.ALPHA.- and 5.BETA.-Series
  作者：Rika Okihara、Kuniko Mitamura、Maki Hasegawa、Megumi Mori、Akina Muto、Genta Kakiyama、Shoujiro Ogawa、Takashi Iida、Miki Shimada、Nariyasu Mano、Shigeo Ikegawa

  DOI：10.1248/cpb.58.344

  日期：——

  Here, we describe the chemical synthesis of the complete sets of 18 novel 3- and 21-monosulfates and their double-conjugated form of tetrahydrocortisol (THF), tetrahydro-11-deoxycortisol (THS), and tetrahydrocortisone (THE) in the 5alpha- and 5beta-series. The principal reactions involved are: (1) selective protection of a specific hydroxy group in substrates; (2) catalytic hydrogenation at C-5 of

  在这里，我们描述了18种新颖的3-和21-单硫酸盐的完整化学合成及其在5alpha-中的四氢皮质醇（THF），四氢-11-脱氧皮质醇（THS）和四氢可的松（THE）的双共轭形式。和5beta系列。涉及的主要反应是：（1）选择性保护底物中的特定羟基；（2）在C-5处将具有10％Pd（OH）（2）/ C的Delta（4）-3-酮类固醇在C-5催化加氢以生成3-oxo-5beta-类固醇并以10％Pd / C进行还原异构化以产生3-氧代-5α-异构体; （3）用Zn（BH（4））（2）和K-Selectride（R）将所得的3-oxo-5beta-和3-oxo-5alpha-类固醇还原为相应的3alpha-羟基化合物，分别;
• Spectroscopic evaluation of synthesized 5β-dihydrocortisol and 5β-dihydrocortisol acetate binding mechanism with human serum albumin and their role in anticancer activity
  作者：Monika Kallubai、Srinivasa P. Reddy、Shreya Dubey、Dhevalapally B. Ramachary、Rajagopal Subramanyam

  DOI：10.1080/07391102.2018.1433554

  日期：2019.2.11

  static quenching, and the binding constants (K) was 4.7 ± .03 × 104 M−1 and 3.9 ± .05 × 104 M−1, and their binding free energies were found to be −6.4 and −6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4 ± .05 × 104 M−1 replaced Dhc, and phenylbutazone 1.5 ± .05 × 104 M−1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA.

  我们的研究集中于合成的5β-二氢皮质醇（Dhc）和5β-二氢皮质醇乙酸盐（DhcA）分子的生物学重要性，对乳腺癌细胞系（MCF-7）正常人胚胎肾细胞系（HEK293）进行了细胞毒性研究，MCF-7细胞的IC 50值分别为28和25μM，而HEK293细胞系未观察到毒性。进一步的实验证明Dhc和DhcA分别诱导了35.6和37.7％的早期凋亡细胞和2.5、2.9％的晚期凋亡细胞，通过TUNEL测定法对细胞死亡的形态学观察表明，Dhc和DhcA诱导了MCF-7细胞的凋亡。观察到HSA–Dhc和HSA–DhcA的复合物为静态猝灭，结合常数（K）为4.7±.03×104  M -1和3.9±.05×10 4  M -1 ，它们的结合自由能分别为-6.4和-6.16 kcal / mol。位移研究证实，利多卡因1.4±.05×10 4  M -1代替了Dhc，苯基丁but 1.5±.05×10 4  M
• USE OF EQUOL FOR TREATING SKIN DISEASES
  申请人：Lephart Edwin Douglas

  公开号：US20100076071A1

  公开（公告）日：2010-03-25

  Equol (7-hydroxy-3(4′hydroxyphenyl)-chroman), the major metabolite of the phytoestrogen daidzein, specifically binds and blocks the hormonal action of 5α-dihydrotestosterone (DHT) in vitro and in vivo. Equol can bind circulating free DHT and sequester it from the androgen receptor, thus altering growth and physiological hormone responses that are regulated by androgens. These data suggest a novel model to explain equol's biological properties. The significance of equol's ability to specifically bind and sequester DHT from the androgen receptor have important ramifications in health and disease and may indicate a broad and important usage for equol in the treatment and prevention of androgen-mediated pathologies of skin and hair. Thus, equol can specifically bind DHT and prevent DHT's biological actions in physiological and pathophysiological processes affecting skin and hair.

  Equol（7-羟基-3（4'-羟基苯基）-色苷）是植物雌激素黄豆异黄酮的主要代谢产物，在体内和体外特异性结合并阻断5α-二氢睾酮（DHT）的激素作用。Equol可以结合循环游离的DHT并将其与雄激素受体分离，从而改变由雄激素调节的生长和生理激素反应。这些数据表明了解释Equol生物特性的新模型。Equol特异性结合和分离DHT对雄激素介导的皮肤和头发病理的治疗和预防具有重要意义，可能表明Equol在健康和疾病中具有广泛和重要的用途。因此，Equol可以特异性结合DHT并防止DHT在影响皮肤和头发的生理和病理生理过程中的生物作用。