甲基孕酮 | 53016-31-2

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药
• 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: 甲基孕酮
• 中文别名: 17-去乙酰基诺孕酯
• 英文名称: 17-deacetylnorgestimate
• 英文别名: 17-deacetyl norgestimate；norelgestromin；d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yne-3-one-3-oxime；17α-hydroxy-13β-ethyl-18,19-dinorpregn-4-ene-20-yn-3-one oxime；d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yne-3-one-oxime；13-ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one 3-oxime；(8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-3-hydroxyimino-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol
• CAS: 53016-31-2
• 化学式: C₂₁H₂₉NO₂
• 分子量: 327.467
• InChiKey: ISHXLNHNDMZNMC-XUDSTZEESA-N

物化性质

• 熔点：
  107-109°C
• 沸点：
  491.9±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：11mg/mL； DMSO：10mg/mL；乙醇：12mg/mL； PBS（pH 7.2）：0.25 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  52.8
• 氢给体数：
  2
• 氢受体数：
  3

制备方法与用途

概述

活性物质甲基孕酮（17-去酰诺孕酯；13-乙基-17-羟基-18,19-二去甲-17-α-孕甾-4-烯-20-炔-3-酮肟）属于孕激素类性激素。

用途

甲基孕酮能够抑制黄体生成素（LH）的释放，从而起到抑制排卵的作用。相比诺孕酯及其代谢产物如3-酮诺孕酯和左炔诺孕酮，甲基孕酮的一个显著优点是其较低的雄激素活性。

生物活性

Norelgestromin是Norgestimate的一种代谢物。

反应信息

• 作为产物：
  描述：

  左炔诺孕酮 在 吡啶 、 盐酸羟胺 作用下， 以 乙腈 为溶剂， 以86%的产率得到甲基孕酮
  参考文献：
  名称：

  Process for the preparation of norelgestromin

  摘要：

  制备诺醇酮或17α-羟基-13β-乙基-18,19-二去甲孕-4-烯-20-炔-3-酮肟的过程，尤其是以晶体形式进行，其E/Z异构体比例在1.3至1.5之间。

  公开号：

  US20070149812A1

文献信息

• [EN] PROCESS FOR THE SYNTHESIS OF HIGH PURITY D-(17ALPHA)-13-ETHYL-17­HYDROXY-18,19-DINORPRE:GN-4-ENE-20-YNE-3-ONE-OXIME<br/>[FR] PROCEDE DE SYNTHESE D'UNE D-(17ALPHA)-13-ETHYL-17-HYDROXY-18,19-DINOR-PREGN-4-ENE-20-YNE-3-ONE-OXIME TRES PURE
  申请人：RICHTER GEDEON VEGYESZET

  公开号：WO2005000868A1

  公开（公告）日：2005-01-06

  The invention relates to a process for the synthesis of high purity d-(17α)-13-ethyl-17­hydroxy-18,19-dinorpregn-4-ene-20-yne-3-one-oxime (further on norelgestromine) via acetylation of d-norgestrel at position 17, oximation of the oxo group at position 3 of the obtained 17-acetoxy derivative, and finally hydrolyzing the acetoxy group at position 17 of the obtained 3-oxime derivative. The process according to our invention is as follows: the starting material, d-(17α-17-hydroxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3­one (d-norgestrel) - purity 93-94 % - is acetylated with acetic anhydride in acetic acid, in the presence of zinc chloride and hydrogen chloride, or 70 % perchloric acid in an inert gas atmosphere, and after completion of the reaction the excess of acetic anhydride and the 'enol acetate' by-product are decomposed with aqueous hydrochioric acid, then the formed d-(17α)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one is isolated from the reaction mixture by addition of ice-water, the precipitated product is filtered off, washed with water, dried, dissolved in dichloromethane or acetone and clarified with silica gel or aluminum oxide and charcoal, after filtration of the clarifier the resulted solution is concentrated and the residue is recrystallized, the obtained d-(17α)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one is reacted either with hydroxylammonium acetate or with hydroxylammonium chloride in the presence of sodium acetate, in acetic acid in nitrogen atmosphere under vigorous stirring for about 1 hour, after completion of the reaction water is added, the precipitated product is filtered off, washed with water, dried and recrystallized, the obtained d-(17α-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one-oxime is hydrolyzed with an equivalent amount of an alkali metal hydroxide in a C1-C4 alkanol solution, in nitrogen atmosphere between a temperature of about 5-38 °C, under vigorous stirring, after completion of the reaction the mixture is diluted with water and the pH of the resulted suspension is adjusted to 7,5-9 with acetic acid, the precipitated product is filtered off, washed with water, dried, the crude product is dissolved in ethanol, clarified with charcoal, and after filtration of the clarifier water is added to the obtained solution, the precipitated high purity d-(17α)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one-oxime is filtered off, washed with water and in given case recrystallized from ethanol.

  该发明涉及一种合成高纯度d-(17α)-13-乙基-17-羟基-18,19-二诺孕烷-4-烯-20-炔-3-酮肟（后称诺尔酮）的过程，通过在17位对d-诺酮基进行乙酰化，在获得的17-乙酰氧衍生物的3位的酮基进行肟化，最后在获得的3-肟衍生物的17位处水解乙酰氧基。根据我们的发明，该过程如下：起始材料，d-(17α-17-羟基-13-乙基-18,19-二诺孕烷-4-烯-20-炔-3-酮（d-诺酮）-纯度93-94％-与乙酸酐在乙酸中，在锌氯化物和氢氯酸或70％高氯酸的惰性气氛中乙酰化，反应完成后，过量的乙酸酐和‘烯醇醋酸酯’副产物通过水盐酸分解，然后通过加入冰水将形成的d-(17α)-17-乙酰氧基-13-乙基-18,19-二诺孕烷-4-烯-20-炔-3-酮从反应混合物中分离，沉淀产物经过过滤、水洗、干燥，溶解于二氯甲烷或丙酮，并用二氧化硅胶或氧化铝和活性炭澄清，澄清剂过滤后浓缩溶液，残渣结晶，获得的d-(17α)-17-乙酰氧基-13-乙基-18,19-二诺孕烷-4-烯-20-炔-3-酮与羟胺醋酸盐或羟胺氯化物在乙酸中与钠醋酸存在下，在氮气氛中激烈搅拌约1小时反应，反应完成后加入水，沉淀产物过滤、水洗、干燥、结晶，获得的d-(17α-17-乙酰氧基-13-乙基-18,19-二诺孕烷-4-烯-20-炔-3-酮肟在C1-C4烷醇溶液中与等量的碱金属氢氧化物在氮气氛中在约5-38°C的温度下激烈搅拌水解，反应完成后用水稀释混合物，结果悬浮液的pH值用乙酸调至7.5-9，沉淀产物过滤、水洗、干燥，粗品溶于乙醇，用活性炭澄清，澄清剂过滤后加入水到获得的溶液，过滤、水洗高纯度d-(17α)-17-乙酰氧基-13-乙基-18,19-二诺孕烷-4-烯-20-炔-3-酮肟。