17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one | 912291-78-2

• 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
• 英文名称: 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one
• 英文别名: 18-nor-17β-hydroxymethyl-17α-methylandrost-1,4,13-triene-3-one；17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-on；20OH-NorMD；17beta-Hydroxymethyl-17alpha-methyl-18-norandrosta-1,4,13-trien-3-one；(8R,9S,10R,17S)-17-(hydroxymethyl)-10,17-dimethyl-6,7,8,9,11,12,15,16-octahydrocyclopenta[a]phenanthren-3-one
• CAS: 912291-78-2
• 化学式: C₂₀H₂₆O₂
• 分子量: 298.425
• InChiKey: GCYZSDGHIVBKJR-QLIIJSOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one 在 三氧化硫吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 18-nor-17β-hydroxymethyl-17α-methylandrost-1,4,13-triene-3-one sulfate
  参考文献：
  名称：

  A new sulphate metabolite as a long-term marker of metandienone misuse

  摘要：

  Metandienone is one of the most frequently detected anabolic androgenic steroids in sports drug testing. Metandienone misuse is commonly detected by monitoring different metabolites excreted free or conjugated with glucuronic acid using gas chromatography mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) after hydrolysis with beta-glucuronidase and liquid-liquid extraction. It is known that several metabolites are the result of the formation of sulphate conjugates in C17, which are converted to their 17-epimers in urine. Therefore, sulphation is an important phase II metabolic pathway of metandienone that has not been comprehensively studied. The aim of this work was to evaluate the sulphate fraction of metandienone metabolism by LC-MS/MS. Seven sulphate metabolites were detected after the analysis of excretion study samples by applying different neutral loss scan, precursor ion scan and SRM methods. One of the metabolites (M1) was identified and characterised by GC-MS/MS and LC-MS/MS as 18-nor-17 beta-hydroxymethyl-17 alpha-methylandrost-1,4,13-triene-3-one sulphate. M1 could be detected up to 26 days after the administration of a single dose of metandienone (5 mg), thus improving the period in which the misuse can be reported with respect to the last long-term metandienone metabolite described (18-nor-17 beta-hydroxymethyl-17 alpha-methylandrost-1,4,13-triene-3one excreted in the glucuronide fraction). (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2013.09.005
• 作为产物：
  描述：

  14-Hydroxy-3β-acetoxyandrost-5-en-17-on 在 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 碘苯二乙酸 、 C₁₃H₁₀O₃Se₂ 、 palladium diacetate 、 zinc trifluoromethanesulfonate 、 镍 、 sodium hydride 、 六氯化钨 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三氟甲烷磺酸甲酯 、 lithium iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 mineral oil 为溶剂， 反应 35.42h， 生成 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one
  参考文献：
  名称：

  17种β-羟甲基-17α-甲基-18-norandrost-13-烯类甾醇的基于CH乙氧基化的化学合成

  摘要：

  在具有独特的17β-羟甲基-17a-甲基-18-nor-13-烯D片段的类固醇的第一个化学合成中，钯催化的CH乙酰氧基化已被提议作为关键转化。此CH功能化步骤对于反转易于获得的合成中间体的四级立体中心的构型至关重要。所开发的方法被用于制备抗兴奋剂分析中作为参考物质所需的甲氧萘醌代谢物，以控制这种雄激素合成代谢类固醇的滥用。

  DOI：

  10.1002/chem.201602957

文献信息

• CYP21-catalyzed production of the long-term urinary metandienone metabolite 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one: a contribution to the fight against doping
  作者：Andy Zöllner、Maria Kristina Parr、Călin-Aurel Drăgan、Stefan Dräs、Nils Schlörer、Frank T. Peters、Hans H. Maurer、Wilhelm Schänzer、Matthias Bureik

  DOI：10.1515/bc.2010.002

  日期：2010.1.1

  product in a single hydroxylation step. The obtained results demonstrate that CYP21 and to a lesser extent also CYP3A4 expressing strains can catalyze this steroid hydroxylation. Subsequent 5 l-scale fermentation resulted in the production and purification of 10 mg of metabolite and its unequivocal structure determination via NMR. The synthesis of this urinary metandienone metabolite via S. pombe-based

  摘要 合成代谢雄激素类固醇是人类运动中最常被误用的药物之一。最近，通过 LC-MS/MS 和 GC-发现了一种以前未知的甲二烯酮尿代谢物 17β-羟甲基-17α-甲基-18-norandrosta-1,4,13-trien-3-one (20OH-NorMD)。小姐。据报道，在服用美二烯酮后长达 19 天的尿样中可检测到这种代谢物。然而，到目前为止，还无法获得该代谢物的纯化参考物质并通过 NMR 确认其结构。筛选了表达不同人类肝脏或类固醇细胞色素 P450 酶的裂殖酵母粟酒裂殖酵母的 11 种重组菌株，以在全细胞生物转化反应中生产这种代谢物。17,17-Dimethyl-18-norandrosta-1,4,13-trien-3-one，化学衍生自美二烯酮，被用作生物转化的底物，因为它可以在单个羟基化步骤中转化为最终产物。获得的结果表明CYP21和在较小程度上还有CYP3A4表达菌株可以催化这种类固醇羟基化。随后的
• Synthesis of 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one: A long-term metandienone metabolite
  作者：Nicolas Kratena、Valentin S. Enev、Günter Gmeiner、Peter Gärtner

  DOI：10.1016/j.steroids.2016.08.013

  日期：2016.11

  The goal of this work was a good-yielding chemical synthesis of a metandienone metabolite which is of interest in doping analysis. 20 beta OH-NorMD (IUPAC: 17 beta-hydroxymethyl-17 alpha-methyl-18-norandrosta-1,4,13-triene-3-one) has been identified as a long-term urinary metabolite which can be detected and attributed to metandienone up to almost 3 weeks after exposure. The chemical synthesis of its epimer 20 alpha OH-NorMD has been described before, as was an enzymatic synthesis of 20 beta OH-NorMD, but no chemical synthesis was published. (C) 2016 Elsevier Inc. All rights reserved.
• C−H Acetoxylation-Based Chemical Synthesis of 17 β-Hydroxymethyl-17 α-methyl-18-norandrost-13-ene Steroids
  作者：Alaksiej L. Hurski、Maryia V. Barysevich、Tatsiana S. Dalidovich、Marharyta V. Iskryk、Nastassia U. Kolasava、Vladimir N. Zhabinskii、Vladimir A. Khripach

  DOI：10.1002/chem.201602957

  日期：2016.9.26

  Palladium‐catalyzed C−H acetoxylation has been proposed as a key transformation in the first chemical synthesis of steroids bearing a unique 17β‐hydroxymethyl‐17α‐methyl‐18‐nor‐13‐ene D‐fragment. This C−H functionalization step was crucial for inverting the configuration at the quaternary stereocenter of a readily available synthetic intermediate. The developed approach was applied to prepare the metandienone

  在具有独特的17β-羟甲基-17a-甲基-18-nor-13-烯D片段的类固醇的第一个化学合成中，钯催化的CH乙酰氧基化已被提议作为关键转化。此CH功能化步骤对于反转易于获得的合成中间体的四级立体中心的构型至关重要。所开发的方法被用于制备抗兴奋剂分析中作为参考物质所需的甲氧萘醌代谢物，以控制这种雄激素合成代谢类固醇的滥用。
• A new sulphate metabolite as a long-term marker of metandienone misuse
  作者：C. Gómez、O.J. Pozo、L. Garrostas、J. Segura、R. Ventura

  DOI：10.1016/j.steroids.2013.09.005

  日期：2013.12

  Metandienone is one of the most frequently detected anabolic androgenic steroids in sports drug testing. Metandienone misuse is commonly detected by monitoring different metabolites excreted free or conjugated with glucuronic acid using gas chromatography mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) after hydrolysis with beta-glucuronidase and liquid-liquid extraction. It is known that several metabolites are the result of the formation of sulphate conjugates in C17, which are converted to their 17-epimers in urine. Therefore, sulphation is an important phase II metabolic pathway of metandienone that has not been comprehensively studied. The aim of this work was to evaluate the sulphate fraction of metandienone metabolism by LC-MS/MS. Seven sulphate metabolites were detected after the analysis of excretion study samples by applying different neutral loss scan, precursor ion scan and SRM methods. One of the metabolites (M1) was identified and characterised by GC-MS/MS and LC-MS/MS as 18-nor-17 beta-hydroxymethyl-17 alpha-methylandrost-1,4,13-triene-3-one sulphate. M1 could be detected up to 26 days after the administration of a single dose of metandienone (5 mg), thus improving the period in which the misuse can be reported with respect to the last long-term metandienone metabolite described (18-nor-17 beta-hydroxymethyl-17 alpha-methylandrost-1,4,13-triene-3one excreted in the glucuronide fraction). (C) 2013 Elsevier Inc. All rights reserved.