3-benzyloxy-14β-(prop-2-en-yl)-des-D-estra-1,3,5(10)-trien-13β-carbaldehyde | 544693-33-6

• 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: 3-benzyloxy-14β-(prop-2-en-yl)-des-D-estra-1,3,5(10)-trien-13β-carbaldehyde
• 英文别名: 16,17-seco-3-benzyloxy-13α-estra-1,3,5(10),16-tetraen-1-al；13α-secoestrone 3-benzyl ether
• CAS: 544693-33-6
• 化学式: C₂₆H₃₀O₂
• 分子量: 374.523
• InChiKey: RUHXPMKJCGVVLU-XPGKHFPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-benzyloxy-14β-(prop-2-en-yl)-des-D-estra-1,3,5(10)-trien-13β-carbaldehyde 在 palladium on activated charcoal jones reagent 、 氢气 作用下， 以 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 20.0 ℃ 、2.0 MPa 条件下， 反应 49.0h， 生成 3-hydroxy-13α-D-homoestra-1,3,5(10)-trien-17a-one
  参考文献：
  名称：

  Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers

  摘要：

  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.

  DOI：

  10.1016/s0039-128x(02)00181-2
• 作为产物：
  描述：

  3-benzyloxy-13α-estra-1,3,5(10)-trien-17-one 在 钾硼氢 、 sodium methylate 作用下， 以 甲醇 、 苯 为溶剂， 反应 81.0h， 生成 3-benzyloxy-14β-(prop-2-en-yl)-des-D-estra-1,3,5(10)-trien-13β-carbaldehyde
  参考文献：
  名称：

  Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers

  摘要：

  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.

  DOI：

  10.1016/s0039-128x(02)00181-2

文献信息

• Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative
  作者：Johanna Szabó、Nóra Jerkovics、Gyula Schneider、János Wölfling、Noémi Bózsity、Renáta Minorics、István Zupkó、Erzsébet Mernyák

  DOI：10.3390/molecules21050611

  日期：——

  angular methyl group and the substitution pattern of the benzyl group of the azide greatly influenced the cell growth-inhibitory potential of the compounds. The 13β derivatives generally proved to be more potent than their 13α counterparts. Introduction of a benzyltriazolylmethyl group onto the 3-OH position seemed to be advantageous. One 13α compound containing an unsubstituted benzyltriazolyl function

  报道了 C-13 差向异构 3-[(1-benzyl-1,2,3-triazol-4-yl) 甲氧基]-d-secoestrones 的合成。三唑类化合物是由 3-(prop-2-inyloxy)-d-secoalcohols 和 p-取代的苄基叠氮化物通过 Cu(I) 催化的叠氮化物-炔烃环加成反应 (CuAAC) 制备的。产品及其前体的抗增殖活性在体外针对一组人粘附的宫颈（HeLa、SiHa 和 C33A）、乳腺（MCF-7、MDA-MB-231、MDA-MB-361 和 T47D）和卵巢(A2780) 细胞系，通过 MTT 分析。角甲基的取向和叠氮化物苄基的取代模式极大地影响了化合物的细胞生长抑制潜力。13β 衍生物通常被证明比它们的 13α 衍生物更有效。将苄基三唑基甲基引入到 3-OH 位置似乎是有利的。一种含有未取代苄基三唑基功能的 13α 化合物对三种细胞系显示出出色的抗增殖活性。
• Synthesis and in vitro antiproliferative evaluation of d-secooxime derivatives of 13β- and 13α-estrone
  作者：Erzsébet Mernyák、Gabriella Fiser、Johanna Szabó、Brigitta Bodnár、Gyula Schneider、Ida Kovács、Imre Ocsovszki、István Zupkó、János Wölfling

  DOI：10.1016/j.steroids.2014.08.015

  日期：2014.11

  and 13α-estrone series. The oximes were modified at three sites in the molecule: the oxime function was transformed into an oxime ether, oxime ester or nitrile group, the propenyl side-chain was saturated and the 3-benzyl ether was removed in order to obtain a phenolic hydroxy function. Triazoles were formed via Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC) from 3-(prop-2-yniloxy)-d-secooximes

  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。
• Electrophile-induced generation of cyclic azomethine imines from steroidal δ-alkenyl hydrazones
  作者：Erzsébet Mernyák、László Márk、Éva Frank、Gyula Schneider、János Wölfling

  DOI：10.1016/j.steroids.2009.01.001

  日期：2009.4

  Novel delta-alkenyl phenylhydrazones were synthesized in both the estrome and the 13 alpha-estrone series. Electrophile-induced cyclizations of alkenyl phenylhydrazones with phenylselenyl bromide furnished cyclic iminium salts, via attack of the irnino nitrogen atom on the intermediate seleniranium ion. Hydride reduction of the iminium salts led to novel aminophenyl-substitued aza-D-homoestrones. The structures of the new products were determined by NMR (one- and two-dimensional) and MALDI-MS techniques, With C-70 fullerenes as matrix in the latter case. (C) 2009 Elsevier Inc. All rights reserved.
• 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.