3-(methoxycarbonyl)estra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide | 124651-20-3

• 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: 3-(methoxycarbonyl)estra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide
• 英文别名: methyl 7β-estra-1,3,5(10)triene-3-carboxylate；methyl 17β-(N-tert-butylcarbamoyl)estra-1,3,5(10)-triene-3-carboxylate；methyl (8S,9S,13S,14S,17S)-17-(tert-butylcarbamoyl)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3-carboxylate
• CAS: 124651-20-3
• 化学式: C₂₅H₃₅NO₃
• 分子量: 397.558
• InChiKey: UBRRHEAKQZTILX-LMHDGWJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(methoxycarbonyl)estra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide 在 sodium hydroxide 、 超重氢 、 cis,trans-dihydrido(acetone)2bis(triphenylphosphine)iridium(III) tetrafluoroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 19.25h， 生成 17β-estra-1,3,5(10)triene-2,4-T2-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of carbon-14 and tritiated steroidal 5α-reductase inhibitors

  摘要：

  17β-[N-(1,1-二甲基乙基)氨基甲酰]雄甾-3,5-二烯-4-14C-3-羧酸（[14C]SK&F 105657）是通过三步序列（叔丁基酰胺化、三氟化、甲氧羰基化）从雄甾-4-烯-3-酮-4-14C-17β-羧酸制备而成的。其A环芳香族类似物17β-[N-(1,1-二甲基乙基)氨基甲酰]雌甾-1,3,5-(10)-三烯-3-羧酸（SK&F 105656）通过铱介导的交换方法用氚标记。

  DOI：

  10.1002/jlcr.2580340702
• 作为产物：
  描述：

  雌酚酮 在 platinum(IV) oxide palladium diacetate 、 2,6-二叔丁基-4-甲基吡啶 、 1,3-双(二苯基膦)丙烷 、 氢气 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 3-(methoxycarbonyl)estra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide
  参考文献：
  名称：

  Steroidal A ring aryl carboxylic acids: a new class of steroid 5.alpha.-reductase inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm00165a009

文献信息

• 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.