3,3-ethylenedioxy-5α,10α-epoxy-17β-cyano-17α-trimethylsilyloxyestr-9(11)-ene | 33403-21-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 英文名称: 3,3-ethylenedioxy-5α,10α-epoxy-17β-cyano-17α-trimethylsilyloxyestr-9(11)-ene
• 英文别名: (1'R,5'S,6'R,9'S,10'S,13'R)-5'-methyl-6'-trimethylsilyloxyspiro[1,3-dioxolane-2,15'-18-oxapentacyclo[11.4.1.01,13.02,10.05,9]octadec-2-ene]-6'-carbonitrile
• CAS: 33403-21-3
• 化学式: C₂₄H₃₅NO₄Si
• 分子量: 429.632
• InChiKey: PSDXUYHICGJWHN-FLINDFHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  64
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,3-ethylenedioxy-5α,10α-epoxy-17β-cyano-17α-trimethylsilyloxyestr-9(11)-ene 在 sulfonic resin "Redex CF" 、 乙二胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.5h， 生成 RU 25593
  参考文献：
  名称：

  Regio and stereospecific synthesis of 11β-substituted 19-norsteroids

  摘要：

  DOI：

  10.1016/0039-128x(81)90039-8
• 作为产物：
  描述：

  (5alpha,10alpha)-5,10-环氧-雌甾-9(11)-烯-3,17-二酮环3-(1,2-乙二基缩醛) 在 咪唑 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 8.25h， 生成 3,3-ethylenedioxy-5α,10α-epoxy-17β-cyano-17α-trimethylsilyloxyestr-9(11)-ene
  参考文献：
  名称：

  Norgestomet 及其 17β-异构体的合成及其对孕酮受体的激动活性的评价

  摘要：

  Norgestomet 是一种合成黄体酮衍生物，用于兽医控制牛的发情和排卵。Norgestomet已广泛用于畜牧业，以促进牛发情同步并提高妊娠率。然而，很少报道用于 Norgestomet 的高度可重复的合成方法。在这里，我们描述了一种合成 Norgestomet 的方法，并进行了定量 NMR 分析以确定产品的纯度。此外，使用碱性磷酸酶测定法评估了合成化合物对孕酮受体 (PRs) 的激动活性。我们合成了纯度为 97.9% 的 Norgestomet，其对 PR 具有激动活性，EC 50值为 4.5 nM。我们还合成了纯度为 92.7% 的 Norgestomet 的 17β-异构体，没有表现出任何 PR 激动活性。所提出的 Norgestomet 合成路线有助于评估食品中残留的 Norgestomet。

  DOI：

  10.1016/j.bmc.2021.116425

文献信息

• Structural modification of 19-norprogesterone I: 17-α-substituted-11-β-substituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents
  申请人：Kim Hyun K.

  公开号：US06900193B1

  公开（公告）日：2005-05-31

  The present invention relates, inter alia, to compounds having the general formula: in which: R 1 is a member selected from the group consisting of —OCH 3 , —SCH 3 , —N(CH 3 ) 2 , —NHCH 3 , —NC 4 H 8 , —NC 5 H 10 , —NC 4 H 8 O, —CHO, —CH(OH)CH 3 , —C(O)CH 3 , —O(CH 2 ) 2 N(CH 3 ) 2 , and —O(CH 2 ) 2 NC 5 H 10 ; R 2 is a member selected from the group consisting of hydrogen, halogen, alkyl, acyl, hydroxy, alkoxy (e.g., methoxy, ethoxy, vinyloxy, ethynyloxy, cyclopropyloxy, etc.), acyloxy (e.g., acetoxy, glycinate, etc.), alkylcarbonate, cypionyloxy, S-alkyl, —SCN, S-acyl and —OC(O)R 6 , wherein R 6 is a functional group including, but not limited to, alkyl (e.g., methyl, ethyl, etc.), alkoxy ester (e.g., —CH 2 OCH 3 ) and alkoxy (—OCH 3 ); R 3 is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; R 4 is a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of ═O and ═N—OR 5 , wherein R 5 is a member selected from the group consisting of hydrogen and alkyl. In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat meningiomas; to treat uterine leiomyomas; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce cervical ripening; to induce labor; and for contraception.

  本发明涉及具有以下一般式的化合物： 其中：R 1 是从羟甲基、硫甲基、二甲胺基、甲胺基、N-丁基、N-戊基、N-丁氧基、甲醛基、羟基乙氧基、乙酰基、氧代乙基二甲胺基和氧代乙基N-戊基等组成的群体中选择的成员；R 2 是从氢、卤素、烷基、酰基、羟基、烷氧基（例如，甲氧基、乙氧基、乙烯氧基、乙炔氧基、环丙氧基等）、乙酰氧基（例如，乙酰氧基、甘氨酸酯等）、烷基碳酸酯、环戊酰氧基、S-烷基、硫氰基、硫酰基和羰基氧基，其中R 6 是包括但不限于烷基（例如，甲基、乙基等）、烷氧酯（例如，-CH 2 OCH 3 ）和烷氧基（-OCH 3 ）在内的官能团；R 3 是从烷基、羟基、烷氧基和乙酰氧基等组成的群体中选择的成员；R 4 是从氢和烷基等组成的群体中选择的成员；X是从═O和═N-OR 5 等组成的群体中选择的成员，其中R 5 是从氢和烷基等组成的群体中选择的成员。 除了提供式I的化合物外，本发明还提供了使用式I的化合物的方法，其中这些化合物有利地用于拮抗内源孕酮；诱导月经；治疗子宫内膜异位症；治疗痛经；治疗内分泌激素依赖性肿瘤；治疗脑膜瘤；治疗子宫平滑肌瘤；治疗子宫肌瘤；抑制子宫内膜增生；诱导宫颈成熟；诱导分娩；以及避孕。
• INDUSTRIAL METHOD FOR THE SYNTHESIS OF 17-ACETOXY-11beta-[4-(DIMETHYLAMINO)-PHENYL]-21-METHOXY-19-NORPREGNA-4,9-DIEN-3,20-DIONE AND THE KEY INTERMEDIATES OF THE PROCESS
  申请人：Bódi József

  公开号：US20100137622A1

  公开（公告）日：2010-06-03

  The present invention relates to a process for the synthesis of the known 17-acetoxy-11-β-[4-(dimethyl amino)-phenyl]-21-methoxy-19-norpregna-4,9-dien-3,20-dione (further on CDB-4124) of formula (I) from 3,3-[1,2-ethandiyl-bis(oxy)]-oestr-5(10),9(11)-dien-17-one of formula (II). Compound CDB-4124 belongs to the group of anti-hormones. The process has the following steps: i) formation of an epoxide; ii) addition of hydrogen cyanide; iii) silylation of a hydroxyl group; iv) reaction with 4-(dimethylamino)-phenyl magnesium bromide Grignard reagent in the presence of CuCl (Teutsch reaction); v) silylation of a hydroxyl group with trimethyl chlorosilane; vi) reaction with diisobutyl aluminum hydride and after addition of acid to the reaction mixture; vii) methoxy-methylation with methoxy-methyl Grignard reagent formed in situ, while hydrolyzing the trimethylsilyl protective groups; viii) oxidation of a hydroxyl group with dicyclohexyl carbodiimide in the presence of dimethyl sulfoxide and a strong organic acid (Swern oxidation), and in given case after purification by chromatography; ix) acetylation of a hydroxyl group with acetic anhydride in the presence of perchloric acid, and in given case, purification by chromatography. The invention also relates to new intermediates of the process.

  本发明涉及一种从式（II）的3,3-[1,2-乙二基基（氧）]-雌-5（10），9（11）-二烯-17-酮合成已知的式（I）的17-乙酰氧基-11-β-[4-（二甲基氨基）-苯基]-21-甲氧基-19-去孕烷-4,9-二烯-3,20-二酮（以下称为CDB-4124）的过程。化合物CDB-4124属于抗激素类。该过程包括以下步骤：i）环氧化反应；ii）氢氰酸加成反应；iii）羟基硅基化反应；iv）在CuCl存在下，与4-（二甲基氨基）-苯基镁溴格氏试剂反应（Teutsch反应）；v）羟基硅基化反应，使用三甲基氯硅烷；vi）与二异丁基铝氢化物反应，加入酸后反应混合物；vii）使用在位形成的甲氧甲基格氏试剂进行甲氧基甲基化反应，同时水解三甲基硅保护基；viii）在二甲基亚砜和强有机酸（Swern氧化）存在下，使用二环己基碳二亚胺氧化羟基，必要时通过色谱纯化；ix）在高氯酸存在下，使用乙酸酐乙酰化羟基，必要时通过色谱纯化。本发明还涉及该过程的新中间体。
• 17-Alpha-substituted-11-beta-substituted-4-aryl and 21-substituted 19-norpregnadienediones as antiprogestational agents
  申请人：The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services

  公开号：EP2348031B9

  公开（公告）日：2016-08-10
• [EN] PROCESS FOR THE SYNTHESIS OF (11 BETA,17ALPHA)-17-ACETOXY-11 -METHYL-19-NORPREGN-4-EN-3,20-DIONE<br/>[FR] PROCÉDÉ POUR LA SYNTHÈSE DE (11 BETA.17ALPHA) -17-ACÉTOXY -1 1-MÉTHYL -19-NORPREGN -4-ÈNE -3,20-DIONE
  申请人：RICHTER GEDEON NYRT

  公开号：WO2015075693A8

  公开（公告）日：2015-12-30
• Synthesis and biological evaluation of partially fluorinated antiprogestins and mesoprogestins
  作者：Klaus Nickisch、Walter Elger、James Cessac、Narkunan Kesavaram、Baishakhi Das、Robert Garfield、Shao-Qing Shi、Olga Amelkina、Reinhard Meister

  DOI：10.1016/j.steroids.2012.09.010

  日期：2013.2

  A series of antiprogestins have been synthesized by partially fluorinating the steroid molecule in positions relevant for receptor binding. By introducing fluorine at the exo-methylene of the 17 spirofuran ring, we obtained partial agonists (mesoprogestins) with significant applications for antiproliferative and antiovulatory treatment strategies in gynecological therapy such as uterine fibroids, endometriosis and heavy menstrual bleeding. Compared to the standard drug RU486, our synthesized compounds exhibited considerable dissociation between antiprogestational and antiglucocorticoid PR receptors. Furthermore, our studies have shown that pure antiprogestins can be generated by partially fluorinating the 17 propenyl and propynl group or by substituting the 4' acetyl phenyl group in the 11 position using trifluromethyl group. (C) 2012 Elsevier Inc. All rights reserved.