17-cyano-3-hydroxyestra-1,3,5(10),16-tetraene 3-methanesulfonate | 19915-19-6

• 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
• 英文名称: 17-cyano-3-hydroxyestra-1,3,5(10),16-tetraene 3-methanesulfonate
• 英文别名: 17-Cyan-oestratetraen-(1.3.5,10.16)-yl-(3)-methansulfonat；[(8S,9S,13S,14S)-17-cyano-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-3-yl] methanesulfonate
• CAS: 19915-19-6
• 化学式: C₂₀H₂₃NO₃S
• 分子量: 357.474
• InChiKey: BWNRVEVFNJPCNZ-YSTOQKLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  75.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  17-cyano-3-hydroxyestra-1,3,5(10),16-tetraene 3-methanesulfonate 在 palladium diacetate 、 palladium on activated charcoal 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 作用下， 以 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 19.0h， 生成 3-(methoxycarbonyl)estra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide
  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
• 作为产物：
  描述：

  雌酚酮 在 zinc(II) iodide 吡啶 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 15.5h， 生成 17-cyano-3-hydroxyestra-1,3,5(10),16-tetraene 3-methanesulfonate
  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

• Estra-1,3,5(10), 16-tetraene derivatives
  申请人：——

  公开号：US20020058651A1

  公开（公告）日：2002-05-16

  Estra-1,3,5(10),16-tetraene derivatives represented by the following formula (I): 1 (wherein R 1 represents hydroxy, alkoxy, or NR 2 R (wherein R 2 and R 3 are the same or different, and each represents hydrogen, straight-chain lower alkyl having 1 to 3 carbon atoms, or branched-chain lower alkyl having 3 to 8 carbon atoms)), or pharmaceutically acceptable salts thereof.

  以下是Estra-1,3,5(10),16-tetraene衍生物的化学式（I）： 其中，R1代表羟基、烷氧基或NR2R（其中R2和R3相同或不同，且每个代表氢、1至3个碳原子的直链低碳基或3至8个碳原子的支链低碳基），或其药学上可接受的盐。
• エストラ−１，３，５（１０），１６−テトラエン誘導体
  申请人：協和醗酵工業株式会社

  公开号：JP2000309599A

  公开（公告）日：2000-11-07

  (57)【要約】\n【課題】ステロイドスルファターゼ阻害作用を示し、ホルモン依存性疾病の治療または予防に有用な作用を有する新規なエストラ-1,3,5(10),16-テトラエン誘導体またはその薬理的に許容される塩を提供すること。\n【解決手段】一般式（Ｉ）\n[式中、Ｒ1はヒドロキシ、アルコキシまたはＮＲ2Ｒ3（式中、Ｒ2及びＲ3は同一または異なって、水素、炭素数１〜３の直鎖状低級アルキルまたは炭素数３〜８の分岐状低級アルキルを表す）を表す］で表されるエストラ-1,3,5(10),16-テトラエン誘導体またはその薬理的に許容される塩を提供する。\n【化１】\n

  (57) [摘要] Јn[问题] 提供新型的雌甾-1,3,5(10),16-四烯衍生物或其药理学上可接受的盐，这些衍生物具有甾体硫酸酯酶抑制活性，可用于治疗或预防激素依赖性疾病。\雌甾-1,3,5(10),16-四烯衍生物由通式（I）\n 代表[其中 R1 代表氢、烷氧基或 NR2R3（R2 和 R3 相同或不同，代表氢、1 至 3 个碳原子的直链低级烷基或 3 至 8 个碳原子的支链低级烷基）]。16-四烯衍生物或其药学上可接受的盐。\Ϯn [Ϯ1] Ϯn
• US6262043B1
  申请人：——

  公开号：US6262043B1

  公开（公告）日：2001-07-17
• US6638923B2
  申请人：——

  公开号：US6638923B2

  公开（公告）日：2003-10-28
• 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.