二(1-金刚烷基)硒化物 | 7548-45-0

• 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: 二(1-金刚烷基)硒化物
• 英文名称: ethinylestradiol 3,17-dimethyl ether
• 英文别名: (8R,9S,13S,14S,17R)-17-ethynyl-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene；3,17β-dimethoxy-17α-ethynylestra-1,3,5(10)-triene；O,O-dimethyl ethinylestradiol；17α-Ethinyl-3.17β-dimethoxy-Δ^1.3.5(10)-oestratrien；3,17-dimethoxy-19-nor-17βH-pregna-1,3,5(10)-trien-20-yne；3,17-Dimethoxy-19-nor-17βH-pregna-1,3,5(10)-trien-20-in；17-Ethynyl-3,17alpha-dimethyoxy-5beta-estra-1,3,5(10)-triene；(8R,9S,13S,14S,17R)-17-ethynyl-3,17-dimethoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene
• CAS: 7548-45-0
• 化学式: C₂₂H₂₈O₂
• 分子量: 324.463
• InChiKey: PGIAEAMVILIUFE-AANPDWTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  二(1-金刚烷基)硒化物 在 N-溴代丁二酰亚胺(NBS) 、 silver nitrate 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以96%的产率得到(8R,9S,13S,14S,17S)-17-(bromoethynyl)-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene
  参考文献：
  名称：

  铜催化的N-炔基化路线生成2-取代的N-炔基吡咯及其环化成Pyrrolo [2,1-c] oxazin-1-ones：Peramine的正式合成

  摘要：

  摘要 炔丙基溴与吡咯的铜催化交叉偶联的各种配体和反应条件的筛选表明，使用菲咯啉配体4,7-二甲氧基-1,10-菲咯啉可提供一系列良好的炔吡咯中等产量。此外，这些吡咯的用途在一系列吡咯并[2,1 - c ] [1,4]恶嗪-1-酮的制备和吡咯天然产物过胺的正式全合成中得到了证明。 炔丙基溴与吡咯的铜催化交叉偶联的各种配体和反应条件的筛选表明，使用菲咯啉配体4,7-二甲氧基-1,10-菲咯啉可提供一系列良好的炔吡咯中等产量。此外，这些吡咯的用途在一系列吡咯并[2,1 - c ] [1,4]恶嗪-1-酮的制备和吡咯天然产物过胺的正式全合成中得到了证明。

  DOI：

  10.1055/s-0036-1588736
• 作为产物：
  描述：

  3-(tert-butyldimethylsilyloxy)-17α-trimethylsilylethynyl-β-estradiol 在 四丁基氟化铵 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 为溶剂， 反应 12.0h， 生成 美雌醇 、 二(1-金刚烷基)硒化物
  参考文献：
  名称：

  Triazole-estradiol analogs: A potential cancer therapeutic targeting ovarian and colorectal cancer

  摘要：

  1,2,3-triazoles have continuously shown effectiveness as biologically active systems towards various cancers, and when used in combination with steroid skeletons as a carrier, which can act as a drug delivery system, allows for a creation of a novel set of analogs that may be useful as a pharmacophore leading to a potential treatment option for cancer. A common molecular target for cancer inhibition is that of the Epidermal Growth Factor Receptor/Mitogen Activated Protein Kinase pathways, as inhibition of these proteins is associated with a decrease in cell viability. Estradiol-Triazole analogs were thus designed using a molecular modeling approach. Thirteen of the high scoring analogs were then synthesized and tested in-vitro on an ovarian cancer cell line (A2780) and colorectal cancer cell line (HT-29). The most active compound, Fz25, shows low micromolar activity in both the ovarian (15.29 ± 2.19 µM) and colorectal lines (15.98 ± 0.39 µM). Mechanism of action studies proved that Fz25 moderately arrests cells in the G1 phase of the cell cycle, specifically inhibiting STAT3 in both cell lines. Additionally, Fz57 shows activity in the colorectal line (24.19 ± 1.37 µM). Inhibition studies in both cell lines show inhibition against various proteins in the EGFR pathway, namely EGFR, STAT3, ERK, and mTOR. To further study their effects as therapeutics, Fz25 and Fz57 were studied against drug efflux proteins, which are associated with drug resistance, and were found to inhibit the ABC transporter P-glycoprotein. We can conclude that these estradiol-triazole analogs provide a key for future studies targeting protein inhibition and drug resistance in cancer.

  DOI：

  10.1016/j.steroids.2021.108950

文献信息

• Steroidal N-Sulfonylimidates: Synthesis and biological evaluation in breast cancer cells
  作者：Yulia A. Volkova、Andrey S. Kozlov、Marya K. Kolokolova、Denis Y. Uvarov、Sergey A. Gorbatov、Olga E. Andreeva、Alexander M. Scherbakov、Igor V. Zavarzin

  DOI：10.1016/j.ejmech.2019.06.048

  日期：2019.10

  Unique derivatives of androstene and estrane series containing N-sulfonylimidate pendants were prepared from 17α-ethynyl steroids via Cu-catalyzed azide–alkyne cycloaddition to tosyl azide in the presence of alcohols. The synthesized compounds were screened for cytotoxicity against human breast cancer cell lines and ERα agonist activity. The hit compound 3,17β-dimethoxy-17α-[iso-propyl-2′-N-tosylacetimidate]estra-1

  在醇存在下，由Cu催化的叠氮化物-炔烃环加成到甲苯磺酰基甲苯中的17种α-乙炔基甾体制备了含有N-磺酰亚胺酰亚胺侧基的雄烯和雌激素系列的独特衍生物。筛选合成的化合物对人乳腺癌细胞系的细胞毒性和ERα激动剂活性。命中化合物3,17- β二甲氧基- 17 α - [异-丙基-2' - Ñ -tosylacetimidate]雌-1,3,5 （10） -三烯（4N）无ERα介导的激素活性，并发现在ERα阳性乳腺癌细胞系中表现出强大的细胞毒性作用。ñ-磺酰亚胺酯4n对三阴性MDA-MB-231乳腺癌细胞显示出高抗增殖能力，而对正常的乳腺上皮细胞无毒。发现化合物4n改变支持肿瘤细胞生长和侵袭性的各种信号传导途径（NF-κB，Slug，细胞周期蛋白D1，ERK）的活性。
• Dual Reactivity of 1,2,3,4‐Tetrazole: Manganese‐Catalyzed Click Reaction and Denitrogenative Annulation
  作者：Hillol Khatua、Sandip Kumar Das、Satyajit Roy、Buddhadeb Chattopadhyay

  DOI：10.1002/anie.202009078

  日期：2021.1.4

  A general catalytic method using a Mn‐porphyrin‐based catalytic system is reported that enables two different reactions (click reaction and denitrogenative annulation) and affords two different classes of nitrogen heterocycles, 1,5‐disubstituted 1,2,3‐triazoles (with a pyridyl motif) and 1,2,4‐triazolo‐pyridines. Mechanistic investigations suggest that although the click reaction likely proceeds through

  据报道，使用基于锰卟啉的催化系统的一般催化方法可实现两种不同的反应（点击反应和脱氮环化反应），并提供两种不同类型的氮杂环，即1,5-二取代的1,2,3-三唑（具有吡啶基）和1,2,4-三唑并吡啶。机理研究表明，尽管点击反应可能是通过离子机理进行的，这与传统的点击反应不同，但脱氮环化反应可能是通过亲电子的茂金属中间体而不是金属金属中间体进行的。总体而言，此方法非常高效，与其他方法相比，具有许多优点。例如，2副产品产生气体。
• Enantioselective Cobalt-Catalyzed Cascade Hydrosilylation and Hydroboration of Alkynes to Access Enantioenriched 1,1-Silylboryl Alkanes
  作者：Shengnan Jin、Kang Liu、Shuai Wang、Qiuling Song

  DOI：10.1021/jacs.1c04248

  日期：2021.8.25

  they are highly valued building blocks in asymmetric synthesis as well as medicinal chemistry. Despite the potential usefulness, efficient synthetic approaches for their preparation are scarce. Seeking to address this deficiency, an enantioselective cobalt-catalyzed hydrosilylation/hydroboration cascade of terminal alkynes has been realized. This protocol constitutes an impressive case of chemo-, regio-

  Enantioenriched 1,1-甲硅烷基硼烷基烷烃具有甲硅烷基和硼烷基，它们都以明确定义的方向连接到相同的立体碳中心。由于这些手性多功能化合物可能提供两个合成手柄，因此它们是不对称合成和药物化学中非常有价值的构建块。尽管具有潜在的用途，但其制备的有效合成方法却很少。为了解决这一缺陷，已经实现了对映选择性钴催化的末端炔烃氢化硅烷化/硼氢化反应级联。该协议构成了一个令人印象深刻的化学、区域和立体选择性案例，其中两种不同的氢官能化事件由一组金属催化剂和配体精确控制，通常需要两个独立的催化系统的操作。对映体富集的 1,1-硅硼烷烷烃的下游转化产生了各种有价值的手性化合物。机理研究表明，本反应经历了高度区域选择性和立体控制的顺序氢化硅烷化和硼氢化过程。
• Metal- and Reagent-Free Intramolecular Oxidative Amination of Tri- and Tetrasubstituted Alkenes
  作者：Peng Xiong、He-Huan Xu、Hai-Chao Xu

  DOI：10.1021/jacs.7b01016

  日期：2017.3.1

  A metal- and reagent-free, electrochemical intramolecular oxidative amination reaction of tri- and tetrasubstituted alkenes has been developed. The electrosynthetic method proceeds through radical cyclization to form the key C-N bond, allowing a variety of hindered tri- and tetrasubstituted olefins to participate in the amination reaction. The result is the efficient synthesis of a host of alkene-bearing

  已开发出一种不含金属和试剂的三取代和四取代烯烃的电化学分子内氧化胺化反应。电合成方法通过自由基环化形成关键的 CN 键，使各种受阻的三和四取代烯烃参与胺化反应。结果是有效合成了大量含烯烃的环状氨基甲酸酯、尿素和内酰胺。
• Grubbs Metathesis Enabled by a Light‐Driven <i>gem</i> ‐Hydrogenation of Internal Alkynes
  作者：Tobias Biberger、Raphael J. Zachmann、Alois Fürstner

  DOI：10.1002/anie.202007030

  日期：2020.10.12

  complexes instigate a light‐driven gem‐hydrogenation of internal alkynes with concomitant formation of discrete Grubbs‐type ruthenium carbene species. This unorthodox reactivity mode is harnessed in the form of a “hydrogenative metathesis” reaction, which converts an enyne substrate into a cyclic alkene. The intervention of ruthenium carbenes formed in the actual gem‐hydrogenation step was proven by the

  [(NHC)(cymene)RuCl 2 ] (NHC=N-杂环卡宾)配合物引发内部炔烃的光驱动宝石-氢化，同时形成离散的 Grubbs 型钌卡宾物质。这种非正统的反应模式以“氢化复分解”反应的形式加以利用，该反应将烯炔底物转化为环状烯烃。在实际宝石氢化步骤中形成的钌卡宾的干预通过分离和结晶表征该系列的一个相当不寻常的代表在二取代的卡宾中心上带有不受限制的烷基而得到证明。