trans-1,4-bis(4-methoxyphenyl)-3-phenyl azetidin-2-one

• 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: trans-1,4-bis(4-methoxyphenyl)-3-phenyl azetidin-2-one
• 英文别名: trans-3-phenyl-1-(4-methoxyphenyl)-4-(4-methoxyphenyl)azetidin-2-one；(±)-trans-1,4-bis(4-methoxyphenyl)-3-phenylazetidin-2-one；(3R,4S)-1,4-bis(4-methoxyphenyl)-3-phenylazetidin-2-one
• 化学式: C₂₃H₂₁NO₃
• 分子量: 359.425
• InChiKey: UAWKPWTZGCUZDJ-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  溴甲苯 、 trans-1,4-bis(4-methoxyphenyl)-3-phenyl azetidin-2-one 在 N,N-二甲基丙烯基脲 、 lithium diisopropyl amide 作用下， 生成 (3S,4S)-3-Benzyl-1,4-bis-(4-methoxy-phenyl)-3-phenyl-azetidin-2-one
  参考文献：
  名称：

  2-Azetidinone Cholesterol Absorption Inhibitors:  Structure−Activity Relationships on the Heterocyclic Nucleus

  摘要：

  A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((-)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure-activity relationships consistent with a well-defined molecular target. The details of these structure-activity relationships and their implications on the nature of the putative pharmacophore are discussed.

  DOI：

  10.1021/jm960405n
• 作为产物：
  描述：

  (4-methoxyphenyl)-[1-(4-methoxyphenyl)meth-(E)-ylidene]amine 在 偶氮二异丁腈 、 三正丁基氢锡 、 phosphorus pentoxide 、 sodium hydride 、 碳酸氢钠 、 sodium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 二甲基亚砜 、 甲苯 、 苯 为溶剂， 反应 62.0h， 生成 trans-1,4-bis(4-methoxyphenyl)-3-phenyl azetidin-2-one
  参考文献：
  名称：

  Azetidin-2,3-dione Synthon for Stereoselective Synthesis ofcis-andtrans-C-3-Alkyl/Aryl Azetidin-2-ones

  摘要：

  1,4-双（4-甲氧基苯基）哌啶-2,3-二酮已经被合成，并作为一种合成子用于C-3-烷基/芳基哌啶-2-酮的立体选择性合成。其中一些被广泛认识为具有胆固醇吸收抑制活性。该合成中的一个关键步骤是，在酮基进行区域选择性的格林纳反应，随后通过还原去除木香酸酯，高度立体选择性地去除羟基。此外，还研究了在碱性条件下，顺式哌啶-2-酮转变为热力学稳定的反式异构体的异构化反应。

  DOI：

  10.1055/s-2005-921746

文献信息

• One-pot synthesis of <i>trans</i>-<font>β</font>-lactams from ferrocenylketene generated by thermal Wolff rearrangement
  作者：Mingshun Liu、Jian’an Wang、Xiaoxi Yuan、Rong Jiang、Nanyan Fu

  DOI：10.1080/00397911.2017.1378358

  日期：2017.12.17

  ABSTRACT A series of β-lactams containing the ferrocene moiety were synthesized through the Staudinger reaction between ferrocenylketene generated by the thermal Wolff rearrangement of the corresponding diazo ketone and various imines. The stereochemical outcome has been investigated and the trans-products were isolated as the main products, opposite to the reported results by Bonini and coworkers

  摘要 通过相应重氮酮的热沃尔夫重排产生的二茂铁基烯酮与各种亚胺之间的施陶丁格反应合成了一系列含有二茂铁部分的β-内酰胺。立体化学结果已被研究，反式产物作为主要产物被分离出来，这与 Bonini 和同事报告的结果相反。(±)-trans-1,4-diphenyl-3-ferrocenylazetidin-2-one (3c) 的绝对构型通过 X 射线分析确定。从反应机理的角度讨论立体选择性。图形概要
• Goel; Thind; Bal, Pharmazie, 2005, vol. 60, # 5, p. 369 - 374
  作者：Goel、Thind、Bal、Mahajan、Kulkarni

  DOI：——

  日期：——
• Novel Method for the Synthesis of b-Lactams by the Reaction of a-Bromocarboxylic Acids with Imines Mediated by Triphenylphosphine
  作者：Yukihiko Hashimoto、Satoshi Kikuchi

  DOI：10.3987/com-05-10661

  日期：——
• 2-Azetidinone Cholesterol Absorption Inhibitors:  Structure−Activity Relationships on the Heterocyclic Nucleus
  作者：John W. Clader、Duane A. Burnett、Mary Ann Caplen、Martin S. Domalski、Sundeep Dugar、Wayne Vaccaro、Rosy Sher、Margaret E. Browne、Hongrong Zhao、Robert E. Burrier、Brian Salisbury、Harry R. Davis

  DOI：10.1021/jm960405n

  日期：1996.1.1

  A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((-)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure-activity relationships consistent with a well-defined molecular target. The details of these structure-activity relationships and their implications on the nature of the putative pharmacophore are discussed.
• Azetidin-2,3-dione Synthon for Stereoselective Synthesis of<i>cis-</i>and<i>trans-</i>C-3-Alkyl/Aryl Azetidin-2-ones
  作者：Abdul Rakeeb Deshmukh、Dharmendra Kumar Tiwari、Vikas K. Gumaste

  DOI：10.1055/s-2005-921746

  日期：——

  1,4-Bis-(4-methoxyphenyl)azetidin-2,3-dione has been prepared and used as a synthon for the stereoselective synthesis of C-3-alkyl/aryl azetidin-2-ones. Some of these are well known for their cholesterol absorption inhibitor activity. A regioselective Grignard reaction at a keto-group followed by highly stereoselective removal of the hydroxyl group via reductive removal of the xanthate ester is a key step in this synthesis. Base-induced isomerization of cis-azetidin-2-ones to the thermodynamically stable trans-isomer was also studied.

  1,4-双（4-甲氧基苯基）哌啶-2,3-二酮已经被合成，并作为一种合成子用于C-3-烷基/芳基哌啶-2-酮的立体选择性合成。其中一些被广泛认识为具有胆固醇吸收抑制活性。该合成中的一个关键步骤是，在酮基进行区域选择性的格林纳反应，随后通过还原去除木香酸酯，高度立体选择性地去除羟基。此外，还研究了在碱性条件下，顺式哌啶-2-酮转变为热力学稳定的反式异构体的异构化反应。