cis-1,4-di-(4-methoxyphenyl)-3-methylazetidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: cis-1,4-di-(4-methoxyphenyl)-3-methylazetidin-2-one
• 英文别名: syn-1,4-bis(p-methoxyphenyl)-3-methylazetidin-2-one；(3R,4R)-1,4-bis(4-methoxyphenyl)-3-methylazetidin-2-one
• 化学式: C₁₈H₁₉NO₃
• 分子量: 297.354
• InChiKey: QROHFJVHRQCLHH-SJKOYZFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 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：

  1-溴-3-苯基丙烷 、 cis-1,4-di-(4-methoxyphenyl)-3-methylazetidin-2-one 在 N,N-二甲基丙烯基脲 、 lithium diisopropyl amide 作用下， 生成 (3S,4S)-1,4-Bis-(4-methoxy-phenyl)-3-methyl-3-(3-phenyl-propyl)-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：

  N-(4-甲氧基亚苄基)-4-甲氧基苯胺 、 丙酰氯 在 三正丁胺 作用下， 以 正庚烷 为溶剂， 反应 4.0h， 生成 cis-1,4-di-(4-methoxyphenyl)-3-methylazetidin-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

文献信息

• Diastereoselective Synthesis of <i>syn</i>-β-Lactams Using Rh-Catalyzed Reductive Mannich-Type Reaction of α,β-Unsaturated Esters
  作者：Motoyuki Isoda、Kazuyuki Sato、Masato Funakoshi、Keiko Omura、Atsushi Tarui、Masaaki Omote、Akira Ando

  DOI：10.1021/acs.joc.5b01233

  日期：2015.8.21

  The combination of Et2Zn and RhCl(PPh3)3 led to the facile generation of a rhodium–hydride complex (Rh–H) that catalyzed the 1,4-reduction of α,β-unsaturated esters. The resulting rhodium enolate performed as a Reformatsky-type reagent and reacted with various imines to give syn-β-lactams in good to excellent yields with high diastereoselectivity.

  Et 2 Zn和RhCl（PPh 3）3的组合导致容易生成铑-氢化物络合物（Rh-H），该络合物催化α，β-不饱和酯的1,4-还原。所得的烯醇铑作为Reformatsky型试剂起作用，并与各种亚胺反应，以良好的非对映异构体收率以优异的产率得到合成的-β-内酰胺。
• Stereoselective one-pot synthesis of β-lactams by Lewis acid promoted condensation of silylketene thioacetals with imines
  作者：Rita Annunziata、Mauro Cinquini、Franco Cozzi、Valentina Molteni、Olaf Schupp

  DOI：10.1016/0040-4020(95)01083-1

  日期：1996.2

  A series of silylketene thioacetals derived from 2-pyridylthioesters have been prepared and the configuration of some of them has been determined by NMR spectroscopy. In the presence of Lewis acids these compounds stereoselectively react with imines to afford β-lactams in a convenient one-pot procedure. An enantioselective β-lactam synthesis promoted by a chiral Lewis acid is also described.

  制备了一系列衍生自2-吡啶基硫酯的甲硅烷基烯酮硫缩醛，其中一些的构型已通过NMR光谱测定。在路易斯酸的存在下，这些化合物与亚胺立体选择性地反应，以方便的一锅法制得β-内酰胺。还描述了由手性路易斯酸促进的对映选择性β-内酰胺合成。
• The synthesis of β-lactams via a one-pot Reformatsky reaction of imines promoted by Zn/Cp2TiCl2 (cat.)
  作者：Lei Chen、Gang Zhao、Yu Ding

  DOI：10.1016/s0040-4039(03)00187-4

  日期：2003.3

  In the presence of Zn/Cp2TiCl2 (cat.) alpha-bromoacetates, gamma-bromocrotonates or alpha-bromomethylacrylates react with imines in one-pot to form beta-lactams, 3-vinyl-beta-lactams or alpha-methylene-gamma-lactams, respectively, at room temperature without the need for pretreatment of the solvent and Zn. (C) 2003 Elsevier Science Ltd. All rights reserved.