(8S,9S,13S,14S,17S)-17-(叔丁基氨基甲酰)-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-3-羧酸 | 124651-01-0

• 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: (8S,9S,13S,14S,17S)-17-(叔丁基氨基甲酰)-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-3-羧酸
• 中文别名: 1-棕榈酰&lt十六烷酰&gt-2-(10-(4-((三氟-甲基)重氮基丙因基)苯基)-9-氧杂十一烷酰)-sn-甘油-3-二氧磷基胆碱
• 英文名称: 17β-(N-tert-butylcarbamoyl)estra-1,3,5(10)-triene-3-carboxylic acid
• 英文别名: estra-1,3,5(10)-triene-3,17β-carboxylic acid 17-tert-butylamide；17β-estra-1,3,5(10)triene-3-carboxylic acid；(8S,9S,13S,14S,17S)-17-(tert-butylcarbamoyl)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3-carboxylic acid
• CAS: 124651-01-0
• 化学式: C₂₄H₃₃NO₃
• 分子量: 383.531
• InChiKey: XDFFJSAVOUJVAR-OCWLBIEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  雌酚酮 在 palladium diacetate 、 palladium on activated charcoal 、 zinc(II) iodide 吡啶 、 sodium hydroxide 、 焦硫酰氟 、 草酰氯 、 1,3-双(二苯基膦)丙烷 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 乙二醇 、 二甲基亚砜 为溶剂， -8.0~160.0 ℃ 、179.27 kPa 条件下， 反应 35.25h， 生成 (8S,9S,13S,14S,17S)-17-(叔丁基氨基甲酰)-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-3-羧酸
  参考文献：
  名称：

  A Novel, Practical Synthesis of Estra-1,3,5(10)-triene-3,17.beta.-dicarboxylic Acid 17-tert-Butylamide (SK&F 105656) from Estrone, via a Palladium-Catalyzed Methoxycarbonylation of a 3-Fluorosulfonate

  摘要：

  The title compound was prepared in nine steps from estrone in 22% overall yield. Each step was performed on a 50-150 gal scale and 3.5 kg of the title compound was prepared. Estrone was converted to its 3-methanesulfonate with methanesulfonyl chloride. The 17-cyanohydrin was prepared using trimethylsilyl cyanide. Dehydration with phosphorus oxychloride/pyridine followed by Pd/C-catalyzed hydrogenation gave the 17 beta-cyano-3-hydroxyestra-1,3,5(10), 16-tetraen-3-yl methanesulfonate derivative stereoselectively. Hydrolysis with sodium hydroxide in ethylene glycol gave a 3/1 beta/alpha mixture of l7-carboxylic acid isomers. Reaction with Vilsmeier reagent and quenching into tert-butylamine, followed by selective crystallization, yielded the desired 3-hydroxyestra-1,3,5(10)-triene-17 beta-carboxylic acid tert-butylamide. Reaction with fluorosulfonic anhydride yielded the S-fluorosulfonate. Palladium-catalyzed carbonylation in the presence of methanol gave the S-carboxylic acid methyl ester, which was saponified to yield SK&F 105656.

  DOI：

  10.1021/jo00101a028

文献信息

• 3-Carboxy-20-keto steroids are dual uncompetitive inhibitors of human steroid 5α-reductase types 1 and 2
  作者：Dennis S. Yamashita、Dennis A. Holt、Hye-Ja Oh、Dinu Shah、Hwa-Kwo Yen、Martin Brandt、Mark A. Levy

  DOI：10.1016/0968-0896(96)00141-1

  日期：1996.9

  Steroidal 3-carboxy-20-ketones have been prepared within two structural series, the androsta-3,5-dienes and the estra-1,3,5-trienes, as potential inhibitors of types 1 and 2 steroid 5 alpha-reductase, the enzyme activity responsible for the final step in biosynthesis of dihydrotestosterone. These compounds are shown to be potent uncompetitive inhibitors of both human recombinant enzyme activities,

  类固醇3-羧基-20-酮已制备为两个结构系列，雄甾烯3,5-二烯和雌激素1,3,5-三烯，作为1型和2型甾体5α-还原酶的潜在抑制剂，负责双氢睾丸激素生物合成最后一步的酶活性。这些化合物显示出是两种人重组酶活性的有效非竞争性抑制剂，从而定义了一类新型的双重类固醇5α-还原酶抑制剂。
• Steroidal A ring aryl carboxylic acids: a new class of steroid 5.alpha.-reductase inhibitors
  作者：Dennis A. Holt、Mark A. Levy、David L. Ladd、Hye Ja Oh、Jill M. Erb、Julie I. Heaslip、Martin Brandt、Brian W. Metcalf

  DOI：10.1021/jm00165a009

  日期：1990.3

  A series of 17 beta-carbamoyl-1,3,5(10)-estratriene-3-carboxylic acids has been prepared and evaluated in vitro as inhibitors of human and rat prostatic steroid 5 alpha-reductase (EC 1.3.1.30). Potent inhibition of the human enzyme, in particular, was observed and preliminary studies using rat enzyme suggest that the inhibition results from the formation of an enzyme-NADP(+)-inhibitor complex. The compounds were synthesized from estrone, generally employing a differentiated bis-triflate carbonylation strategy.
• REDUCTION OF BOAR ODOR IN MEAT
  申请人：PFIZER INC.

  公开号：EP0688219B1

  公开（公告）日：2002-02-06
• US5604214A
  申请人：——

  公开号：US5604214A

  公开（公告）日：1997-02-18
• A Novel, Practical Synthesis of Estra-1,3,5(10)-triene-3,17.beta.-dicarboxylic Acid 17-tert-Butylamide (SK&F 105656) from Estrone, via a Palladium-Catalyzed Methoxycarbonylation of a 3-Fluorosulfonate
  作者：Michael A. McGuire、Edmund Sorenson、Franklin W. Owings、Theodore M. Resnick、Margaret Fox、Neil H. Baine

  DOI：10.1021/jo00101a028

  日期：1994.11

  The title compound was prepared in nine steps from estrone in 22% overall yield. Each step was performed on a 50-150 gal scale and 3.5 kg of the title compound was prepared. Estrone was converted to its 3-methanesulfonate with methanesulfonyl chloride. The 17-cyanohydrin was prepared using trimethylsilyl cyanide. Dehydration with phosphorus oxychloride/pyridine followed by Pd/C-catalyzed hydrogenation gave the 17 beta-cyano-3-hydroxyestra-1,3,5(10), 16-tetraen-3-yl methanesulfonate derivative stereoselectively. Hydrolysis with sodium hydroxide in ethylene glycol gave a 3/1 beta/alpha mixture of l7-carboxylic acid isomers. Reaction with Vilsmeier reagent and quenching into tert-butylamine, followed by selective crystallization, yielded the desired 3-hydroxyestra-1,3,5(10)-triene-17 beta-carboxylic acid tert-butylamide. Reaction with fluorosulfonic anhydride yielded the S-fluorosulfonate. Palladium-catalyzed carbonylation in the presence of methanol gave the S-carboxylic acid methyl ester, which was saponified to yield SK&F 105656.