3-(tert-butyldimethylsiloxy)-17α-ethynylestradiol | 39845-30-2

• 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-(tert-butyldimethylsiloxy)-17α-ethynylestradiol
• 英文别名: 3-(tert-butyldimethylsilyloxy)-17α-ethynyl-β-estradiol；3-O-tert-butyldimethylsilyl-17α-ethynyl-β-estradiol；(8R,9S,13S,14S,17R)-3-[tert-butyl(dimethyl)silyl]oxy-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol
• CAS: 39845-30-2
• 化学式: C₂₆H₃₈O₂Si
• 分子量: 410.672
• InChiKey: CSZIVCGZGDDUNR-RPWISQQKSA-N

物化性质

• 沸点：
  470.3±45.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.29
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(tert-butyldimethylsiloxy)-17α-ethynylestradiol 在 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 tris(dibenzylideneacetone)dipalladium (0) copper(l) iodide 、 caesium carbonate 、 二乙胺 、 三苯基膦 作用下， 以 甲苯 为溶剂， 生成 tert-butyl N-[5-[2-[(8R,9S,13S,14S,17S)-3-[tert-butyl(dimethyl)silyl]oxy-17-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]ethynyl]pyridin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate
  参考文献：
  名称：

  合成17-α-取代的雌二醇-吡啶-2-基肼共轭物，作为在水中用Alberto络合物fac- [Re（OH2）3（CO）3] +标记的有效配体。

  摘要：

  （99m）Tc-雌二醇放射性药物的开发将有利于检测雌激素受体阳性的乳腺肿瘤。与有机金属三羰基-Tc（I）和相关的Re（I）配合物共轭的雌二醇衍生物能够实现高受体结合亲和力，但是在水中合成放射性标记配合物的有效方法尚不可用。我们对2-肼基吡啶作为Tc和Re的配体的合成的兴趣使我们研究了Pd催化卤代吡啶底物与肼基二甲酸二叔丁酯的胺化反应。2-和4-取代的卤代吡啶底物均经过与偶氮二甲酸二叔丁酯的CN偶联反应，生成Boc保护的吡啶肼衍生物。仅高度亲电子的3-吡啶卤化物被转化为肼。Boc保护的5-溴吡啶-2-基肼底物3是通过在2，5-二溴吡啶的2-位进行区域选择性取代而制备的。使用Sonogashira和Suzuki / Miyaura偶联反应分别以高收率合成1和2，将这种双功能螯合物连接到雌二醇的17alpha位置的乙炔基或乙烯基上。在酸性条件下将1脱保护得到肼盐酸盐25。通过用fac- [Re（

  DOI：

  10.1021/jo034780g
• 作为产物：
  描述：

  在 叔丁基锂 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 3-(tert-butyldimethylsiloxy)-17α-ethynylestradiol
  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

• Palladium(II)-Catalyzed Site-Selective C(sp³ )−H Alkynylation of Oligopeptides: A Linchpin Approach for Oligopeptide-Drug Conjugation
  作者：Tao Liu、Jennifer X. Qiao、Michael A. Poss、Jin-Quan Yu

  DOI：10.1002/anie.201706367

  日期：2017.8.28

  C(sp3)−H alkynylation of oligopeptides was developed with tetrabutylammonium acetate as a key additive. Through molecular design, the acetylene motif served as a linchpin to introduce a broad range of carbonyl‐containing pharmacophores onto oligopeptides, thus providing a chemical tool for the synthesis and modification of novel oligopeptide–pharmacophore conjugates by C−H functionalization. Dipeptide

  以乙酸四丁基铵为关键添加剂，开发了钯 (II) 催化的寡肽 C(sp 3 )−H 炔基化反应。通过分子设计，乙炔基序作为关键，将多种含羰基的药效团引入到寡肽上，从而为通过CH官能化合成和修饰新型寡肽-药效团缀合物提供了化学工具。通过该方法合成了与粪甾烷醇和雌二醇的二肽缀合物，其在向核激素受体过度表达的肿瘤细胞靶向药物递送方面具有潜在的应用。
• Steroidal Affinity Labels of the Estrogen Receptor. 2. 17.alpha.-[(Haloacetamido)alkyl]estradiols
  作者：Driss El Garrouj、Sigrid Aliau、Andre Aumelas、Jean-Louis Borgna

  DOI：10.1021/jm00013a011

  日期：1995.6

  alpha-electrophilic estradiol derivatives to be potent affinity labels of the receptor, we prepared four 17 alpha-[(haloacetamido)alkyl]estradiols. Three were bromoacetamides differing at the alkyl substituent (methyl, ethyl, or propyl), and the last was an [(iodoacetamido)propyl]estradiol prepared under both nonradioactive and 3H-labeled forms. Although their affinities for the estrogen receptor were very low

  在先前的研究中，我们描述了17α-[（溴乙酰氧基）烷基/炔基]雌二醇对羔羊子宫雌激素受体的亲和标记。但是，这些化合物的内在受体烷基化活性可能由于在含雌激素受体的组织提取物中较差的水解稳定性而受到很大的阻碍。因此，（i）开发不易水解的受体的亲和标记，（ii）指定17α-亲电子雌二醇衍生物作为受体的有效亲和标记的结构要求，我们制备了四个17α-[（卤代乙酰胺基） ）烷基]雌二醇。三个是在烷基取代基（甲基，乙基或丙基）上不同的溴乙酰胺，最后一个是以非放射性和3H标记形式制备的[（碘乙酰胺基）丙基]雌二醇。尽管它们对雌激素受体的亲和力很低（雌二醇的亲和力从0.008％降至0.02％），但由于它们不可逆地抑制羔羊子宫细胞质中的[3H]雌二醇特异性结合，因此它们似乎是该受体的有效亲和标记。化合物的作用是时间，pH和浓度依赖性的，对于活性较低的化合物和活性较高的化合物，分别在0℃和pH 8.5时> 50％和>
• Target-selective degradation of proteins by a light-activated 2-phenylquinoline-estradiol hybrid
  作者：Akane Suzuki、Kana Tsumura、Takeo Tsuzuki、Shuichi Matsumura、Kazunobu Toshima

  DOI：10.1039/b708947c

  日期：——

  A designed 2-phenylquinoline-estradiol hybrid effectively and selectively degraded the target transcription factor, human estrogen receptor-alpha (hER-alpha), which has a high affinity with the estradiol moiety, under long-wavelength UV photo-irradiation, without additives and under neutral conditions.

  设计的2-苯基喹啉-雌二醇杂合体在长波紫外光辐照下，无需添加任何添加剂，即可有效，选择性地降解与雌二醇部分具有高亲和力的目标转录因子人雌激素受体-α（hER-alpha）。在中性条件下。
• Molecular design, chemical synthesis, and biological evaluation of agents that selectively photo-degrade the transcription factor estrogen receptor-α
  作者：Kana Tsumura、Akane Suzuki、Takeo Tsuzuki、Shuho Tanimoto、Hajime Kaneko、Shuichi Matsumura、Masaya Imoto、Kazuo Umezawa、Daisuke Takahashi、Kazunobu Toshima

  DOI：10.1039/c1ob05629h

  日期：——

  2-Phenylquinoline (1) degraded proteins under photo-irradiation with long-wavelength UV light without additives and under neutral conditions. We designed and synthesized a 2-phenylquinoline-estrogen receptor-α (ER-α) agonist (hybrid 2) and a 2-phenylquinoline-ER-α antagonist (hybrid 3) containing estradiol and 4-hydroxytamoxifen moieties, respectively. These 2-phenylquinoline hybrids effectively and selectively

  2-苯基喹啉（1）在无添加剂的长波长紫外光和中性条件下，在光辐照下降解了蛋白质。我们设计并合成了分别含有雌二醇和4-羟基他莫昔芬部分的2-苯基喹啉-雌激素受体-α（ER-α）激动剂（杂交2）和2-苯基喹啉-ER-α拮抗剂（杂交3）。这些2-苯基喹啉杂种有效地和选择性地光降解了目标转录因子ER-α，后者对雌二醇和4-羟基他莫昔芬具有很高的亲和力。在玻璃容器和MCF-7乳腺癌细胞中均检测了靶标选择性光降解，这取决于ER-α的生长。另外，2-苯基喹啉-雌二醇杂化物2在没有光照射的情况下，它起着ER-α激动剂的作用，促进了MCF-7的生长，而由于ER-α的光降解，它在光照射后抑制了MCF-7细胞的生长。相反，由于4-羟基他莫昔芬部分对ER-α的拮抗作用，在没有光照射的情况下，2-苯基喹啉-4-羟基他莫昔芬杂种3抑制MCF-7细胞的生长，并且在光辐照后显着抑制细胞4-羟基他莫昔芬部分的双重拮抗作用和ER-α的光降解引起细胞生长。
• Novel 17α-ethynylestradiol derivatives: Sonogashira couplings using unprotected phenylhydrazines
  作者：Jeffrey B Arterburn、Kalla Venkateswara Rao、Marc C Perry

  DOI：10.1016/s0040-4039(99)02205-4

  日期：2000.2

  The Pd/Cu catalyzed coupling of 17α-ethynylestradiol with halogenated amino-substrates was investigated. Iodophenylhydrazine and its protected derivatives reacted with 17α-ethynylestradiol to give 4-hydrazinophenyl derivatives without any degradation of the hydrazine group. Unprotected 3-, and 4-iodoaniline reacted similarly to produce the aminophenyl-derivatives. Protection of the amino group of halogenated

  研究了17d-乙炔基雌二醇与卤代氨基底物的Pd / Cu催化偶联。碘苯肼及其受保护的衍生物与17α-乙炔基雌二醇反应生成4-肼基苯基衍生物，而肼基团没有任何降解。未保护的3-和4-碘苯胺类似地反应以产生氨基苯基衍生物。炔烃偶联反应需要保护卤代苄胺的氨基，以避免苄胺底物竞争性邻位钯缩合。