4-(4-methoxyphenyl)-4-[4-(pivaloyloxy)phenyl]-3-phenylbut-1-ene | 886463-36-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 4-(4-methoxyphenyl)-4-[4-(pivaloyloxy)phenyl]-3-phenylbut-1-ene
• 英文别名: 4-(4-methoxyphenyl)-3-phenyl-4-(4-pivaloyloxyphenyl)but-1-ene；1-(4-methoxyphenyl)-2-phenyl-1-(4-pivaloyloxyphenyl)-3-butene；[4-[1-(4-methoxyphenyl)-2-phenylbut-3-enyl]phenyl] 2,2-dimethylpropanoate
• CAS: 886463-36-1
• 化学式: C₂₈H₃₀O₃
• 分子量: 414.544
• InChiKey: MZRYQKMYERBJJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-methoxyphenyl)-4-[4-(pivaloyloxy)phenyl]-3-phenylbut-1-ene 在 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 以93%的产率得到E/Z-1-(4-hydroxyphenyl)-1-(4-methoxyphenyl)-2-phenylbutene
  参考文献：
  名称：

  Synthesis of the new pseudo-symmetrical tamoxifen derivatives and their anti-tumor activity

  摘要：

  Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-60 human acute promyelocytic leukemia, whereas 16 possesses medium activity against the cell line and 17 has no effect on the cell viability. The agarose gel electrophoresis for DNA cleavage showed the cell death might be induced by apoptosis. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.037
• 作为产物：
  描述：

  4-甲酰基苯基特戊酸酯 、 (E)-trimethyl(3-phenylallyl)silane 以75的产率得到4-(4-methoxyphenyl)-4-[4-(pivaloyloxy)phenyl]-3-phenylbut-1-ene
  参考文献：
  名称：

  Process for Production of Lasofoxifene or Analogue Thereof

  摘要：

  本发明公开了一种生产拉索福辛、纳福西汀或其类似物的新工艺，该工艺步骤较少，效率高，实用性优越。用于生产拉索福辛或其类似物的中间体化合物是由式（4）表示的化合物。可以通过在一步中耦合三个组分来使用由式（1）到（3）表示的化合物作为起始化合物，从而制备由式（4）表示的化合物。

  公开号：

  US20090012314A1

文献信息

• An expeditious synthesis of tamoxifen, a representative SERM (selective estrogen receptor modulator), via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole
  作者：Isamu Shiina、Yoshiyuki Sano、Kenya Nakata、Masahiko Suzuki、Toshikazu Yokoyama、Akane Sasaki、Tomoko Orikasa、Tomomi Miyamoto、Masahiko Ikekita、Yukitoshi Nagahara、Yoshimune Hasome

  DOI：10.1016/j.bmc.2007.09.008

  日期：2007.12

  three-component coupling reaction among aromatic aldehydes, cinnamyltrimethylsilane, and aromatic nucleophiles using HfCl(4) as a Lewis acid catalyst to produce 3,4,4-triarylbutene, that is also a valuable intermediate of the tamoxifen derivatives. The former strategy requires a total of 10 steps from the aldol formation to the final conversion to tamoxifen, whereas the latter needs only three or four steps

  开发了抗癌药物他莫昔芬及其衍生物的两种新的合成途径。第一条路线涉及苄基苯基酮与乙醛的醛醇缩合反应，然后在Cl（2）Si（OTf）（2）存在下用苯甲醚进行Friedel-Crafts取代，生成1,1,2-三芳基-3-乙酰氧基丁烷，他莫昔芬衍生物的前体。第二种方法利用HfCl（4）作为路易斯酸催化剂，利用芳香族醛类，肉桂基三甲基硅烷和芳香族亲核体之间的新型三组分偶联反应生成3,4,4-三芳基丁烯，这也是他莫昔芬衍生物的重要中间体。前一种策略从形成醛醇到最终转化为他莫昔芬共需要10个步骤，后者仅需三到四个步骤即可生产他莫昔芬和屈洛昔芬，包括侧链部分的安装和碱诱导的双键迁移以形成四取代的烯烃结构。这种合成策略似乎不仅可以制备他莫昔芬衍生物，而且可以制备其他SERM（选择性雌激素受体调节剂），包括雌激素依赖性乳腺癌和骨质疏松症药物，是一种新的实用途径。
• An Expeditious Synthesis of Lasofoxifene and Nafoxidine via the Novel Three-component Coupling Reaction
  作者：Yoshiyuki Sano、Kenya Nakata、Takafumi Otoyama、Sei Umeda、Isamu Shiina

  DOI：10.1246/cl.2007.40

  日期：2007.1

  The simple and efficient synthesis of lasofoxifene (4), a possible candidate for alleviating osteoporosis, via the novel three-component coupling reaction among 4-pivaloyloxybenzal-dehyde (5), cinnamyltrimethylsilane (6), and anisole in the presence of HfCl 4 is illustrated. The successive cationic cyclization of the coupling product, olefin formation, and migration of the double-bond are performed

  在 HfCl 4 存在下，通过 4-新戊酰氧基苯甲醛 (5)、肉桂基三甲基硅烷 (6) 和苯甲醚之间的新型三组分偶联反应，简单有效地合成 lasofoxifene (4)，一种可能的缓解骨质疏松症的候选药物是插图。进行偶联产物的连续阳离子环化、烯烃形成和双键迁移，以通过非常简洁的程序提供拉索昔芬 (4) 和萘福昔定 (3) 的常见合成中间体。
• Synthesis of Lasofoxifene, Nafoxidine and Their Positional Isomers via the Novel Three-Component Coupling Reaction
  作者：Kenya Nakata、Yoshiyuki Sano、Isamu Shiina

  DOI：10.3390/molecules15106773

  日期：——

  A Lewis acid-mediated three-component coupling reaction was successfully applied for the synthesis of lasofoxifene (1), nafoxidine (2), and their positional isomers, inv-lasofoxifene (3) and inv-nafoxidine (4). In the presence of HfCl4, the desired one-pot coupling reaction among 4-pivaloyloxybenzaldehyde (5), cinnamyltrimethylsilane (6), and anisole proceeded to afford the corresponding 3,4,4-triaryl-1-butene 7 in high yield. The iodocarbocyclization of the coupling product and the successive elimination of hydrogen iodide forming the olefin part, followed by the migration of the double-bond afforded the common synthetic intermediate of lasofoxifene (1) and nafoxidine (2) via a very concise procedure. Additionally, the syntheses of their positional isomers inv-lasofoxifene (3) and inv-nafoxidine (4) were also achieved through very convenient protocols.

  路易斯酸介导的三组分偶联反应被成功地用于合成拉索昔芬（1）、萘福昔定（2）以及它们的位置异构体 inv-lasofoxifene (3) 和 inv-nafoxidine (4)。在 HfCl4 存在下，4-pivaloyloxy 苯甲醛 (5)、肉桂基三甲基硅烷 (6) 和苯甲醚发生了所需的一锅偶联反应，以高产率得到了相应的 3,4,4-三芳基-1-丁烯 7。耦合产物的碘代碳环化和形成烯烃部分的碘化氢的连续消除，以及随后的双键迁移，通过非常简洁的程序得到了拉索昔芬（1）和萘福昔定（2）的常见合成中间体。此外，它们的位置异构体 inv-lasofoxifene (3) 和 inv-nafoxidine (4) 也是通过非常简便的方法合成的。
• Dihydronaphthalene compound and use thereof
  申请人：Tokyo University of Science Educational Foundation Administrative Organization

  公开号：US08183235B2

  公开（公告）日：2012-05-22

  Disclosed is a compound represented by the formula (I) below as a dihydronaphthalene compound having a chemical structure which is excellent in production efficiency when compared with lasofoxifene and nafoxidine. This compound is useful as a proteasome inhibitor and/or an antitumor agent. (In the formula, two —(CH2)l—N(R1) (R2) groups represent a same substituent; R1 and R2 each represents a hydrogen atom, or a same or different alkyl group; or alternatively, R1 and R2 may combine together to form a monocyclic heterocyclic ring with a nitrogen atom having them or additionally together with one or more atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom; R3, R4 and R5 each represents one or more substituents selected from a hydrogen atom, an alkyl group, an acyl group, an alicyclic group, an aromatic group, a halogen atom, an acyloxy group, a cyano group and a nitro group; l represents an integer of 2-5; n represents an integer of 1-4; m represents an integer of 1-5; and q represents an integer of 1-3.)

  本发明公开了一种化合物，其化学结构为二氢萘衍生物，化学式（I）如下，与拉索福辛和纳福西汀相比，该化合物的生产效率更高。该化合物可用作蛋白酶抑制剂和/或抗肿瘤剂。（在公式中，两个—（CH2）l—N（R1）（R2）基团代表同一取代基；R1和R2分别代表氢原子或相同或不同的烷基基团；或者，R1和R2可以结合在一起形成一个单环杂环，其中含有它们或另外与选择的一个或多个原子一起选择自氧原子、硫原子和氮原子的氮原子；R3、R4和R5各代表从氢原子、烷基基团、酰基基团、脂环基团、芳基基团、卤素原子、酰氧基团、氰基团和硝基团中选择的一个或多个取代基；l代表2-5的整数；n代表1-4的整数；m代表1-5的整数；q代表1-3的整数。）
• Process for production of lasofoxifene or analogue thereof
  申请人：Tokyo University of Science Educational Foundation Administrative Organization

  公开号：US08193394B2

  公开（公告）日：2012-06-05

  Disclosed is a novel process for production of lasofoxifene, nafoxidine or an analogue thereof, which comprises reduced number of reaction steps, has a high efficiency, and is practically advantageous. For the production of lasofoxifene or an analogue thereof, a compound represented by the formula (4) is used as an intermediate. The compound represented by the formula (4) can be produced using compounds represented by the formulae (1) to (3) as starting compounds by performing the coupling of the three components in one step.

  本发明公开了一种新型的拉索福辛、纳福西定或其类似物的生产工艺，该工艺步骤少、效率高、实用性优越。在生产拉索福辛或其类似物时，使用化合物（4）表示的中间体。化合物（4）可以通过使用化合物（1）到（3）表示的起始化合物，在一步反应中耦合三个组分来制备。