3β-乙酰氧基-5β-雄甾烷-17-酮 | 1098-12-0

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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: 3β-乙酰氧基-5β-雄甾烷-17-酮
• 英文名称: 3β-acetoxy-(5ξ)-androstan-17-one
• 英文别名: Epiandrosteron-acetat；(3beta,8xi,9xi,14xi)-17-Oxoandrostan-3-yl acetate；[(3S,10S,13S)-10,13-dimethyl-17-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-yl] acetate
• CAS: 1098-12-0；1164-95-0；1239-31-2；1482-78-6；4820-41-1；13383-12-5；19915-13-0；95043-80-4；95119-02-1；95119-06-5
• 化学式: C₂₁H₃₂O₃
• 分子量: 332.483
• InChiKey: FDCINQSOYQUNKB-OAHYLZCJSA-N

物化性质

• 熔点：
  169-173°C
• 沸点：
  424.6±45.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

制备方法与用途

用途：用作避孕药炔诺酮的中间体。

生产方法：

1. 将乙醇、盐酸羟胺和吡啶搅拌并回流溶解后，加入醋酸妊娠双烯醇酮，继续回流3小时。冷却至5℃，过滤，滤饼用乙醇洗涤，并用水洗至中性，干燥后得到醋酸妊娠双烯酮肟。
2. 将上述产物与苯、吡啶一同搅拌冷却至0℃左右，缓缓加入氧氯化磷与苯的混合液，在4-7℃反应3小时。再加盐酸进行水解，在5℃左右保温2小时。
3. 静置后分去水层，将苯层用水洗涤至中性，并进行水蒸汽蒸馏。待苯蒸尽后，有淡黄色固体析出，过滤、用水洗涤至中性，于80℃干燥，最终得到去氢表雄酮醋酸酯。

反应信息

• 作为反应物：
  描述：

  3β-乙酰氧基-5β-雄甾烷-17-酮 在 钾硼氢 、 甲基三辛基氯化铵 作用下， 以 水 为溶剂， 反应 1.5h， 以99%的产率得到
  参考文献：
  名称：

  水不溶性高熔点有机底物水反应的实用解决方案

  摘要：

  对于难溶性高熔点（VSSHMP）有机底物进行水反应的问题，已经开发出一种实用的解决方案，该方法需要机械搅拌底物，相应的试剂，水，催化性Aliquat 336的混合物和沙子。当包括类固醇，酮，醛，芳族化合物和生物碱的底物的熔点为约200℃时，反应可以在20℃下进行。底物溶解度可以低至1×10 -10 mol L -1。

  DOI：

  10.1039/c2gc16328d

文献信息

• Novel C-17-Heteroaryl Steroidal Cyp17 Inhibitors/Antiandrogens, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
  申请人：Brodie Angela

  公开号：US20080280864A1

  公开（公告）日：2008-11-13

  Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP 17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer.

  描述了类固醇C-17苯并咫唑、嘧啶咪唑咪唑（氮杂苯并咫唑）和二氮杂苯并咪唑。还描述了它们的合成方法，其中包括3β-乙酰氧基-17-氯-16-甲酰基雄甾-5,16-二烯或其类似物和苯并咫唑或嘧啶咪唑亲核试剂的亲核乙烯“加成-消除”取代反应步骤的方法，以及17-碘雄甾-5,16-二烯-3β-醇或其类似物与三丁基锡二氮杂苯基的钯催化交叉偶联反应的方法。这些化合物是人类CYP 17酶的有效抑制剂，同时也是野生型和突变雄激素受体（AR）的有效拮抗剂。这些化合物对于治疗人类前列腺癌是有用的。
• Novel C-17-Heteroaryl Steroidal Cyp17 Inhibitors/Antiandrogens: Synehesis, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
  申请人：Brodie Angela

  公开号：US20100137269A1

  公开（公告）日：2010-06-03

  Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer.

  本文描述了类固醇C-17苯并咪唑，嘧啶并咪唑（氮杂苯并咪唑）和二氮杂苯。还描述了它们的合成方法，其中包括3β-乙酰氧基-17-氯-16-甲酰基雄甾-5，16-二烯或其类似物与苯并咪唑或嘧啶并咪唑亲核试剂进行亲核性乙烯基“加成-消除”取代反应的步骤，以及17-碘雄甾-5，16-二烯-3β-醇或其类似物与三丁基锡基二氮杂苯进行钯催化的交叉偶联反应的方法。这些化合物是人CYP17酶的有效抑制剂，同时也是野生型和突变雄激素受体（AR）的有效拮抗剂。这些化合物可用于治疗人类前列腺癌。
• ALTERING STEROID METABOLISM FOR TREATMENT OF STEROID-DEPENDENT DISEASE
  申请人：THE CLEVELAND CLINIC FOUNDATION

  公开号：US20160310509A1

  公开（公告）日：2016-10-27

  A method of treating steroid-dependent disease such as prostate cancer in a subject is described that includes administering a therapeutically effective amount a CYP17A inhibitor and an effective amount of a 5-α-reductase inhibitor to the subject.
• NOVEL C-17-HETEROARYL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS, IN VITRO BIOLOGICAL ACTIVITIES, PHARMACOKINETICS AND ANTITUMOR ACTIVITY
  申请人：The University of Maryland, Baltimore

  公开号：US20180036320A1

  公开（公告）日：2018-02-08

  Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer.
• US7875599B2
  申请人：——

  公开号：US7875599B2

  公开（公告）日：2011-01-25