3,17β-dihydroxy-17α-(2'-phenyl-1'-ethyn-1'-yl)estra-1,3,5(10)-triene | 2685-03-2

• 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: 3,17β-dihydroxy-17α-(2'-phenyl-1'-ethyn-1'-yl)estra-1,3,5(10)-triene
• 英文别名: 17α-21-phenyl-19-norpregna-1,3,5(10)-triene-20-yne-3,17β-diol；17α-(phenylethynyl)-3,17β-estradiol；17α-(phenylethynyl)-17β-estradiol；17α-(2'-phenylethynyl)estradiol；17α-(phenylethynyl)estradiol；(8R,9S,13S,14S,17S)-13-methyl-17-(2-phenylethynyl)-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol
• CAS: 2685-03-2
• 化学式: C₂₆H₂₈O₂
• 分子量: 372.507
• InChiKey: AJLVFMYGVRSQRI-JMTTVTNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,17β-dihydroxy-17α-(2'-phenyl-1'-ethyn-1'-yl)estra-1,3,5(10)-triene 在 silver(I) acetate 、 氯化铵 、 锌 作用下， 以 ammonium hydroxide 、 异丙醇 为溶剂， 反应 18.0h， 以80%的产率得到(17α,20Z)-21-(phenyl)-19-norpregna-1,3,5(10),20-tetraene-3,17β-diol
  参考文献：
  名称：

  Stereochemical probes for the estrogen receptor: Synthesis and receptor binding of (17α,20EZ)-21-phenyl-19-norpregna-1,3,5(10), 20-tetraene-3,17β-diols

  摘要：

  Previous studies from our laboratory using 17 alpha-E- and 17 alpha-Z-halovinyl and phenylthiovinyl estradiols demonstrated a marked preference for the Z stereochemistry and a significant steric tolerance for the Z-vinyl substituent. To further explore the extent of that stereochemical preference and steric tolerance we have prepared stereoselectively the 17 alpha-E- and 17 alpha-Z-phenylvinyl estradiols (E- and Z-styrylestradiols). The results, in addition to demonstrating a facile preparation of the target compounds, supported the previously observed stereochemical and steric effects. The relative binding affinities for the Z isomer were 3-4-fold greater than the E isomer at both 4 degrees C and 25 degrees C, and only one-half to one-fourth those of estradiol under similar conditions. The developing model for ligand-accessible space within the estrogen receptor suggests that Z-phenylvinyl estradiols may provide interesting and useful probes for mapping the receptor. (C) 1996 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(96)00201-2
• 作为产物：
  描述：

  雌酚酮 、 苯乙炔 在 甲基锂 作用下， 生成 3,17β-dihydroxy-17α-(2'-phenyl-1'-ethyn-1'-yl)estra-1,3,5(10)-triene
  参考文献：
  名称：

  用于开发荧光雌激素受体配体的 17α -雌二醇的取代类似物

  摘要：

  为了成功开发出高亲和力荧光团-雌二醇偶联物，荧光团必须连接到雌二醇分子上对其与受体结合干扰最小的位置。基于文献先例和我们早期使用小 17 α 侧链的工作，我们专注于 17 α 取代基作为荧光团连接的模型。在本报告中，我们描述了 19 种雌二醇类似物的合成和雌激素受体结合亲和力，它们在 17 α 位取代了较大的侧链（6 到 11 个碳），其中一些可能经过合成修饰以连接荧光团。这些类似物是通过雌酮-17 β-环氧乙烷 3-苄基醚的亲核裂解和随后的脱苄基（4 到 18），通过炔烃（21 到 24）的交叉偶联合成的，通过 17 α-乙炔雌二醇 3,17-双（四氢吡喃基醚）的烷基化和随后的酸性水解（25 至 28），或通过将雌酮与适当的芳基/炔基锂试剂（29、30 和 32）或与苄基溴化镁（ 31)。使用标准竞争测定法测定这些新合成的类似物对雌激素受体（大鼠子宫）的相对结合亲和力。结果表明，侧链中迁

  DOI：

  10.1016/0039-128x(91)90070-c

文献信息

• Nickel-Catalyzed Reductive [2+2] Cycloaddition of Alkynes
  作者：Santiago Cañellas、John Montgomery、Miquel À. Pericàs

  DOI：10.1021/jacs.8b09677

  日期：2018.12.19

  The nickel-catalyzed synthesis of tetrasubstituted cyclobutenes from alkynes is reported. This transformation is uniquely promoted by the use of a primary aminophosphine, an unusual ligand in nickel catalysis. Mechanistic insights for this new transformation are provided, and postreaction modifications of the cyclobutene products to stereodefined cyclic and acyclic compounds are reported, including

  报道了镍催化从炔烃合成四取代环丁烯的方法。这种转化是通过使用伯氨基膦（镍催化中一种不常见的配体）来独特促进的。提供了这种新转化的机理见解，并报道了环丁烯产物对立体定义的环状和无环化合物的反应后修饰，包括表-特鲁昔酸的合成。
• Synthesis of 4-[¹⁸F]fluoroiodobenzene and its application in sonogashira cross-coupling reactions
  作者：Frank R. Wüst、Torsten Kniess

  DOI：10.1002/jlcr.709

  日期：2003.7

  convenient access to 4-[18F]fluoroiodobenzene in 13–70% yield using conventional heating or microwave activation. The Sonogashira cross-coupling of 4-[18F]fluoroiodobenzene with terminal alkynes gave the corresponding 4-[18F]fluorophenylethynyl-substituted compounds [18F]-9, [18F]-10 and [18F]-13 in yields up to 88% within 20 min of starting from 4-[18F]fluoroiodobenzene. Copyright © 2003 John Wiley

  Sonogashira 交叉偶联反应在 18F 化学中的首次应用已经开发出来。该反应的例子是末端炔烃（乙炔基环戊基甲醇 6、17α-乙炔基-3,17β-雌二醇 7 和 17α-乙炔基-3-甲氧基-3,17β-雌二醇 8）与 4-[18F] 氟碘苯的交叉偶联. 4,4'-二碘二芳基碘鎓盐用作合成 4-[18F] 氟碘苯的前体，使用常规加热或微波活化可以方便地获得 4-[18F] 氟碘苯，产率为 13-70%。4-[18F] 氟碘苯与末端炔烃的 Sonogashira 交叉偶联得到相应的 4-[18F] 氟苯基乙炔基取代化合物 [18F]-9、[18F]-10 和 [18F]-13，产率高达 88%从 4-[18F] 氟碘苯开始的 20 分钟内。版权所有 © 2003 John Wiley & Sons, Ltd.
• Structure−Activity Relationships of 17α-Derivatives of Estradiol as Inhibitors of Steroid Sulfatase
  作者：Roch P. Boivin、Van Luu-The、Roger Lachance、Fernand Labrie、Donald Poirier

  DOI：10.1021/jm0001166

  日期：2000.11.1

  inhibit steroid sulfatase activity may be a rewarding approach to the treatment of androgeno-sensitive and estrogeno-sensitive diseases. In the present study, we report the chemical synthesis and biological evaluation of a new family of steroid sulfatase inhibitors. The inhibitors were designed by adding an alkyl, a phenyl, a benzyl, or a benzyl substituted at position 17alpha of estradiol (E(2)), a C18-steroid

  类固醇硫酸酯酶或甾基硫酸酯酶是广泛分布在人体组织中的微粒体酶，其催化硫酸化的3-羟基类固醇水解为相应的游离活性3-羟基类固醇。由于雄激素和雌激素可能是从血液中可用的脱氢表雄酮硫酸盐（DHEAS）和硫酸雌酮（E（1）S）开始在癌细胞内合成的，因此使用抑制类固醇硫酸酯酶活性的治疗剂可能是一种有益的方法。雄激素敏感性和雌激素敏感性疾病的治疗。在本研究中，我们报告了甾族硫酸酯酶抑制剂新家族的化学合成和生物学评估。通过添加在C18类固醇的雌二醇（E（2））的17α位上取代的烷基，苯基，苄基或苄基来设计抑制剂 使用均质的JEG-3细胞或转染到HEK-293细胞中的类固醇硫酸酯酶进行酶分析。我们观察到，疏水取代基可强烈抑制类固醇硫酸酯酶，而亲水取代基则较弱。尽管在17α-位的疏水基团增加了抑制活性，但位阻因素却起到了相反的作用。如17alpha-decyl-E（2）和17alpha-dodecyl-E（
• Syntheses and affinities of novel organometallic-labeled estradiol derivatives: a structure-affinity relationship
  作者：Hani El Amouri、Anne Vessieres、Dominique Vichard、Siden Top、Michel Gruselle、Gerard Jaouen

  DOI：10.1021/jm00095a006

  日期：1992.8

  Two series of novel estradiol derivatives, including cationic species, labeled with organometallic fragments Cr(CO)3, Cp*Ru+, or Cp*Rh2+ [Cp* = eta-5-C5(CH3)5] either in the 17-alpha-position or on the A-ring were synthesized, and their relative binding affinities (RBA) for the estradiol receptor were determined. The Ru(II) and the Rh(III) cationic derivatives were obtained as stable salts with the following counter anions (BF4-, PF6-, CF3SO3-). The satisfactory RBA values obtained for most complexes belonging to the 17-alpha series confirm that this position tolerates the presence of bulky neutral species. For instance, complex 4, in which the organometallic fragment Cr(CO)3 Was attached to the phenyl ring of the 17-alpha-phenylethynyl fragment, exhibited an RBA value of 24%, very similar to that of the uncomplexed estrogen derivative 3. Surprisingly, the analogous cationic species 6 had no affinity for the estradiol receptor. This unprecedented result shows that the hormone binding site of the estrogen receptor does not tolerate the presence of a positive charge in the 17-alpha-position of the steroid. On the other hand, the alpha-face of the A-ring of estradiol did tolerate positively charged organometallic fragments bearing bulky substituents althoug the RBA value tended to decrease with increasing charge. The counterion in these cationic derivatives also affected binding affinity. For instance, the Ru(II) species 7a containing an CF3SO3- ion exhibited a reasonable RBA value (5.8%) compared to analogous species 13 with a PF6- ion (RBA of only 0.1%). Moreover, the triflate counteranion preserved the phenolic form of the A-ring of the estrogen derivative whereas the PF6- derivative was unstable and rapidly converted into the dienonylic form in buffer. The compared RBAs of the neutral and cationic species illustrate the preferences of the receptor hormone binding site in accepting or rejecting species of hydrophobic or hydrophilic character.
• 17α -Substituted analogs of estradiol for the development of fluorescent estrogen receptor ligands
  作者：Mohammad Salman、B.R. Reddy、Pete Delgado、Philip L. Stotter、Letitia C. Fulcher、Gary C. Chamness

  DOI：10.1016/0039-128x(91)90070-c

  日期：1991.7

  literature precedent and on our earlier work with small 17 alpha side chains. In this report, we describe syntheses and estrogen receptor binding affinities of 19 analogs of estradiol substituted in the 17 alpha position with larger side chains (of six to 11 carbons), some of which may be synthetically modified to link a fluorophore. These analogs were synthesized either by nucleophilic cleavage of estrone-17

  为了成功开发出高亲和力荧光团-雌二醇偶联物，荧光团必须连接到雌二醇分子上对其与受体结合干扰最小的位置。基于文献先例和我们早期使用小 17 α 侧链的工作，我们专注于 17 α 取代基作为荧光团连接的模型。在本报告中，我们描述了 19 种雌二醇类似物的合成和雌激素受体结合亲和力，它们在 17 α 位取代了较大的侧链（6 到 11 个碳），其中一些可能经过合成修饰以连接荧光团。这些类似物是通过雌酮-17 β-环氧乙烷 3-苄基醚的亲核裂解和随后的脱苄基（4 到 18），通过炔烃（21 到 24）的交叉偶联合成的，通过 17 α-乙炔雌二醇 3,17-双（四氢吡喃基醚）的烷基化和随后的酸性水解（25 至 28），或通过将雌酮与适当的芳基/炔基锂试剂（29、30 和 32）或与苄基溴化镁（ 31)。使用标准竞争测定法测定这些新合成的类似物对雌激素受体（大鼠子宫）的相对结合亲和力。结果表明，侧链中迁