3-methoxy-16,17-seco-13α-estra-1,3,5(10),16-tetraen-17-al | 474890-22-7

• 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-methoxy-16,17-seco-13α-estra-1,3,5(10),16-tetraen-17-al
• 英文别名: (1S,2R,4aS,10aR)-7-methoxy-2-methyl-1-prop-2-enyl-3,4,4a,9,10,10a-hexahydro-1H-phenanthrene-2-carbaldehyde
• CAS: 474890-22-7
• 化学式: C₂₀H₂₆O₂
• 分子量: 298.425
• InChiKey: WLYPPQXNJMAQEV-ZRNYENFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methoxy-16,17-seco-13α-estra-1,3,5(10),16-tetraen-17-al 在 盐酸羟胺 、 sodium acetate 作用下， 以 水 、 乙腈 为溶剂， 反应 1.0h， 以94%的产率得到3-methoxy-14β-(prop-2-en-yl)-des-D-13α-estra-1,3,5(10)-trien-13β-carbaldehyde oxime
  参考文献：
  名称：

  13β-和13α-雌酮的d-开环肟衍生物的合成和体外抗增殖评价

  摘要：

  d-Secooximes 是由 13β- 和 13α-雌酮系列中的 d-secoaldehydes 合成的。肟在分子中的三个位点被修饰：肟官能团转化为肟醚、肟酯或腈基团，丙烯基侧链饱和，去除3-苄基醚以获得酚羟基官能团. 三唑类化合物是由 3-(prop-2-yniloxy)-d-secooximes 和苄基叠氮化物通过 Cu(I) 催化的叠氮化物-炔烃环加成反应 (CuAAC) 形成的。所有产品都通过 MTT 分析在体外评估了对一组人贴壁细胞系（HeLa、MCF-7、A2780 和 A431）的抗增殖活性。其中一些表现出亚微摩尔 IC50 值的活性，优于参考药物顺铂。结构修饰导致细胞生长抑制特性的显着差异。流式细胞术表明，最有效的药物之一导致细胞周期阻断。

  DOI：

  10.1016/j.steroids.2014.08.015
• 作为产物：
  描述：

  16-hydroxymethylene-3-methoxy-13α-estra-1,3,5(10)-trien-17-one 在 氢氧化钾 、 钾硼氢 作用下， 以 甲醇 为溶剂， 反应 31.0h， 生成 3-methoxy-16,17-seco-13α-estra-1,3,5(10),16-tetraen-17-al
  参考文献：
  名称：

  16-羟甲基-3-甲氧基-13α-estra-1,3,5(10)-trien-17-ols的立体选择性卤化及其溶剂分解研究

  摘要：

  16α-羟甲基-3-甲氧基-13α-estra-1,3,5(10)-trien-17beta-ol (3a) 和 16β-羟甲基-3-甲氧基-13α-estra-1,3 的主要羟基功能,5(10)-trien-17alpha-ol (4a) 被立体选择性地转化为良好的离去基团。在 16-卤甲基或 16-甲苯磺酰氧基甲基衍生物的碱性甲醇分解中，以高收率获得了一种新的 D-seco-13α-雌酮衍生物。

  DOI：

  10.1016/s0039-128x(03)00048-5

文献信息

• Electrophile- and Lewis acid-induced nitrone formation and 1,3-dpolar cycloaddition reactions in the 13α- and 13β-estrone series
  作者：Erzsebet Mernyak、Judit Huber、Gabriella Benedek、Roland Pfoh、Stephan Rühl、Gyula Schneider、János Wölfling

  DOI：10.3998/ark.5550190.0011.b10

  日期：——

  3-methyl ether undergo intramolecular 1,3-dipolar cycloaddition reactions with BF3•OEt2 as catalyst, furnishing isoxazolidines. The reactions of the 13α- and 13β-estrone oximes with electrophiles lead to cyclic nitrones in high yields via attack of the oxime nitrogen on the intermediate halonium ions. In the intermolecular cycloadditions of 16-halomethyl nitrones to N-phenylmaleimide, single condensed aza-D-homo

  13α-雌酮3-甲基醚的δ-烯基肟以BF3•OEt2为催化剂进行分子内1,3-偶极环加成反应，得到异恶唑烷。13α- 和 13β- 雌酮肟与亲电子试剂的反应通过肟氮对中间体卤离子的攻击导致高产率的环硝酮。在 16-卤甲基硝酮与 N-苯基马来酰亚胺的分子间环加成反应中，形成具有高化学和立体选择性的单一稠合氮杂-D-高异恶唑烷。
• Stereoselective Synthesis of Condensed Aza-<scp>d</scp>-homo-estrone Derivatives by 1,3-Dipolar Cycloaddition
  作者：János Wölfling、Erzsébet Mernyák、Gabriella Benedek、Gyula Schneider

  DOI：10.1055/s-2005-862390

  日期：——

  The halogen-induced intramolecular formation of 13a- and 13β-estrone nitrones, followed by 1,3-dipolar cycloaddition reactions with N-phenylmaleimide (NPM) stereoselectively furnished halogen-containing condensed heterocyclic D-homosteroids.

  卤素诱导分子内形成 13a- 和 13β-雌酮硝酮，然后与 N-苯基马来酰亚胺 (NPM) 进行 1,3-偶极环加成反应，立体选择性地提供含卤素的稠合杂环 D-同类固醇。
• Stereoselective Approach to some Novel 16-Methylated and 16-Halomethylated Tetrahydropyran and δ-Lactone Derivatives in both the Normal and the 13α-Estrone Series
  作者：Gyula Schneider、Éva Frank、Erzsébet Mernyák、János Wölfling

  DOI：10.1055/s-2002-34947

  日期：——

  D-secoestrone alcohol and secoestrone carboxylic acid in both the normal and the 13a-estrone series are reported. The ring-closure reactions furnished substituted, new oxa-D-homoestrone derivatives stereoselectively.

  报告了正常和 13a-雌酮系列中不饱和 D-癸烯酮醇和癸烯雌酮羧酸的 3-甲基醚的分子内环化。闭环反应立体选择性地提供了取代的新氧杂-D-高雌酮衍生物。
• Synthesis of antiproliferative 13α-d-homoestrones via Lewis acid-promoted one-pot Prins–Ritter reactions of d-secosteroidal δ-alkenyl-aldehydes
  作者：Judit Huber、János Wölfling、Gyula Schneider、Imre Ocsovszki、Mónika Varga、István Zupkó、Erzsébet Mernyák

  DOI：10.1016/j.steroids.2015.07.004

  日期：2015.10

  A simple one-pot Prins-Ritter route was developed for the synthesis of 16-acylamino-17a-hydroxy-D-homoestrone 3-benzyl and 3-methyl ethers in the 13 alpha-estrone series. The D-secosteroidal delta-alkenyl-aldehydes were allowed to react with different nitriles in the presence of BF3.OEt2 as a Lewis acid catalyst. Prins cyclizations afforded 17a-hydroxy-16-carbenium ions, which underwent Ritter reactions with nitriles, leading to 16 alpha- or 16 beta-acylamino derivatives. A side-product in which a dihydro-1,3-oxazine was bridged to six-membered ring D at positions 16 alpha,17a alpha, was formed in each reaction. The antiproliferative properties of the novel 13 alpha-D-homosteroids were determined on a panel of human adherent cancer cell lines (HeLa, MCF-7, T47D, MDA-MB-231, MDA-MB-361, A2780 and A431) by means of MTT (3-[4,5-d imethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays. Some compounds proved to be more effective (with submicromolar IC50 values) than the reference agent cisplatin. One of the most potent compounds substantially increased the rate of tubulin polymerization. Cell cycle analyses by flow cytometry indicated a concentration-dependent accumulation of the G2/M cell population. (C) 2015 Elsevier Inc. All rights reserved.
• Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers
  作者：János Wölfling、Erzsébet Mernyák、Éva Frank、George Falkay、Árpád Márki、Renáta Minorics、Gyula Schneider

  DOI：10.1016/s0039-128x(02)00181-2

  日期：2003.3

  An effective epimerization of the normal estrone 3-methyl and 3-benzyl ethers by using o-phenylenediamine and AcOH made the possibility for facile entry into the 13alpha-estrone series. Combination of this synthetic methodology with an isolation step carried out by means of the Girard-P reagent, the corresponding ethers of 13-epi-estrone were obtained in excellent yields. The 3-hydroxy and 3-methoxy D-homoestrone derivatives in both the normal and the 13alpha-estrone series were then synthesized and tested in vitro in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities (RBAs) are lower than that of the reference compound 3,17beta-estradiol. The progesterone receptor-binding affinities of the four D-homo derivatives were also tested showing low values for 13alpha-D-homoestrone and its 3-methyl ether. Pharmacologically, these 13alpha-D-homoestrone derivatives are estrogen receptor-selective molecules. (C) 2002 Elsevier Science Inc. All rights reserved.