(E,Z)-4-[4-(2-dimethylaminoethoxy)phenyl]-3,4-diphenyl-but-3-en-2-ol | 556834-77-6

• 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: (E,Z)-4-[4-(2-dimethylaminoethoxy)phenyl]-3,4-diphenyl-but-3-en-2-ol
• 英文别名: 4-(4-(2-(dimethylamino)ethoxy)phenyl)-3,4-diphenylbut-3-en-2-ol；α-hydroxytamoxifen；(E)-alpha-Hydroxy tamoxifen;alpha-OHTAM；4-[4-[2-(dimethylamino)ethoxy]phenyl]-3,4-diphenylbut-3-en-2-ol
• CAS: 556834-77-6
• 化学式: C₂₆H₂₉NO₂
• 分子量: 387.522
• InChiKey: BPHFBQJMFWCHGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E,Z)-4-[4-(2-dimethylaminoethoxy)phenyl]-3,4-diphenyl-but-3-en-2-ol 在 4-甲基苯磺酸吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氯化碳 、 乙酸乙酯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 以16.667%的产率得到
  参考文献：
  名称：

  光氧化还原催化的内部烯烃到四取代的烯烃的C H芳基化：他莫昔芬的合成

  摘要：

  可见光诱导的直接C-H芳基化S，S -官能化的烯烃的内部，即，α氧代烯酮二硫和类似物，已经有效地与芳基重氮盐（ARN实现2 BF 4）作为偶联和Ru（联吡啶）3 Cl 2 ·6H 2 O在环境温度下作为光敏剂。研究了通过烷硫基和吸电子官能团激活内部烯烃CH键的策略。该合成方案已成功应用于包括他莫昔芬在内的全碳四取代烯烃的合成。

  DOI：

  10.1021/acs.orglett.7b03223
• 作为产物：
  描述：

  (E,Z)-4-[4-(2-dimethylaminoethoxy)phenyl]-3,4-diphenyl-but-3-en-2-one 在 sodium tetrahydroborate 、 cerium(III) chloride 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以91%的产率得到(E,Z)-4-[4-(2-dimethylaminoethoxy)phenyl]-3,4-diphenyl-but-3-en-2-ol
  参考文献：
  名称：

  SYNTHESIS OF α-HYDROXYTAMOXIFEN AND ITS 4-HYDROXY ANALOG

  摘要：

  DOI：

  10.1080/00304940309355839

文献信息

• Identification of Tamoxifen−DNA Adducts Formed by α-Sulfate Tamoxifen and α-Acetoxytamoxifen
  作者：Lakkaraju Dasaradhi、Shinya Shibutani

  DOI：10.1021/tx960114h

  日期：1997.2.1

  were synthesized as proposed active metabolites of tamoxifen that react with DNA. alpha-Acetoxytamoxifen was prepared as a model-activated form to produce a reactive carbocation. Calf thymus DNA was reacted with alpha-hydroxytamoxifen or the activated forms of tamoxifen, and tamoxifen-DNA adducts were analyzed by a 32P-postlabeling method. The reactivity of alpha-sulfate trans-tamoxifen to DNA was much

  合成了α-硫酸盐反式他莫昔芬和α-硫酸盐顺他莫昔芬，作为他莫昔芬与DNA反应的活性代谢产物。将α-乙酰氧他莫昔芬制备为模型激活形式，以产生反应性碳正离子化。小牛胸腺DNA与α-羟基他莫昔芬或他莫昔芬的活化形式反应，并通过32P后标记法分析他莫昔芬-DNA加合物。α-硫酸反式他莫昔芬对DNA的反应性比α-羟基他莫昔芬的反应性高得多。由α-乙酰氧基他莫昔芬和α-硫酸盐顺式他莫昔芬诱导的他莫昔芬-DNA加合物的形成分别比α-羟基他莫昔芬高1100倍和1600倍。α-硫酸他莫昔芬和α-乙酰氧基他莫昔芬均对2'-脱氧鸟苷具有高反应性。HPLC分离了dG-他莫昔芬的四种反应产物，并通过质子和质子磁共振波谱进行了表征。首先洗脱的馏分1和2被鉴定为dG-N2-他莫昔芬反式的差向异构体。馏分3和4被鉴定为dG-N2-他莫昔芬的顺式差向异构体。当DNA与α-乙酰氧基他莫昔芬体外反应时，检测到dG-N2-他莫昔
• Reaction of the tamoxifen cation and the bis-(4-methoxyphenyl)methyl cation in aqueous solutions containing 2<i>'</i>-deoxyguanosine
  作者：Robert A McClelland、Cristina Sanchez、Effiette Sauer、Sinisa Vukovic

  DOI：10.1139/v02-011

  日期：2002.3.1

  The competition between 2'-deoxyguanosine (dG) and water has been quantitatively evaluated for the allylic carbocation derived from tamoxifen and for the stabilized diarylmethyl cation (bis-(4-methoxyphenyl)methyl). Both systems were examined by the competition kinetics method, in which the products were quantitatively analyzed after the S_N1 solvolysis of the corresponding acetate esters in aqueous solutions containing the nucleoside. The principal product of the reaction of both cations with dG is the adduct at the NH₂ group, a characteristic of delocalized carbocations. The tamoxifen cation was also examined by laser flash photolysis, with absolute rate constants for the reaction with dG and water being obtained and converted into rate constant ratios. The principal result of this study is that there is a three orders of magnitude difference in the reactivity of these cations towards the neutral form of dG and its conjugate base. Under acidic conditions where the reaction occurs with neutral dG, the guanine–water selectivity is low. Even at relatively high concentrations of dG, the majority of the product is alcohol derived from the water reaction. At pH 10 to 11, in contrast, dG is present as the anion and this is highly competitive. Yields of adduct as high as 90% can be attained. A consequence of the large difference in reactivities is that at neutral pH the majority of the reaction of the cation with dG is actually occurring via the small amount of conjugate base present. A further feature of the results is that the NH₂ adduct is the predominant stable product from the anion. To explain the high rate constant for the reaction forming this product, a mechanism is proposed whereby one of the protons of the NH₂ group is transferred to N1 as the N2-cation bond is forming.Key words: guanine, DNA adduct, carbocation, tamoxifen.

  2'-脱氧鸟苷（dG）与水之间的竞争已经定量评估了从他莫昔芬衍生的烯丙基碳离子和稳定的二芳基甲基阳离子（双（4-甲氧基苯基）甲基）中。这两个系统都通过竞争动力学方法进行了研究，在其中，在含有核苷的水溶液中，对应的乙酸酯经S_N1溶解后，产物被定量分析。两个阳离子与dG的反应的主要产物是NH₂基团的加合物，这是离域化碳离子的特征。他莫昔芬阳离子也通过激光闪光光解法进行了研究，获得了与dG和水反应的绝对速率常数，并转化为速率常数比。这项研究的主要结果是，在这些阳离子与dG和其共轭碱的中性形式之间的反应性存在三个数量级的差异。在反应发生于中性dG的酸性条件下，鸟嘌呤-水选择性较低。即使在相对高浓度的dG下，大多数产物也是来自水反应的醇。相比之下，在pH 10到11之间，dG以阴离子的形式存在，这是高度竞争的。可以获得高达90％的加合物收率。反应性差异巨大的一个结果是，在中性pH下，阳离子与dG的大多数反应实际上是通过少量存在的共轭碱进行的。结果的另一个特征是，NH₂加合物是来自阴离子的主要稳定产物。为了解释形成该产物的反应速率常数高的原因，提出了一种机理，其中NH₂基团的一个质子在N1形成N2-阳离子键时被转移。关键词：鸟嘌呤，DNA加合物，碳离子，他莫昔芬。
• Photoredox-Catalyzed C–H Arylation of Internal Alkenes to Tetrasubstituted Alkenes: Synthesis of Tamoxifen
  作者：Quannan Wang、Xiaoge Yang、Ping Wu、Zhengkun Yu

  DOI：10.1021/acs.orglett.7b03223

  日期：2017.11.17

  Visible-light-induced direct C–H arylation of S,S-functionalized internal alkenes, that is, α-oxo ketene dithioacetals and analogues, has been efficiently realized with aryldiazonium salts (ArN2BF4) as coupling partners and Ru(bpy)3Cl2·6H2O as photosensitizer at ambient temperature. The strategy to activate the internal olefinic C–H bond by both the alkylthio and electron-withdrawing functional groups

  可见光诱导的直接C-H芳基化S，S -官能化的烯烃的内部，即，α氧代烯酮二硫和类似物，已经有效地与芳基重氮盐（ARN实现2 BF 4）作为偶联和Ru（联吡啶）3 Cl 2 ·6H 2 O在环境温度下作为光敏剂。研究了通过烷硫基和吸电子官能团激活内部烯烃CH键的策略。该合成方案已成功应用于包括他莫昔芬在内的全碳四取代烯烃的合成。
• SYNTHESIS OF α-HYDROXYTAMOXIFEN AND ITS 4-HYDROXY ANALOG
  作者：M. R. Lashley、C. W. Dicus、K. Brown、M. H. Nantz

  DOI：10.1080/00304940309355839

  日期：2003.4