(+/-)-(4R^*,5R^*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one | 109838-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (+/-)-(4R^*,5R^*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one
• 英文别名: (+/-)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one；(2R,3R)-1-methyl-5-oxo-3-phenylpyrrolidine-2-carbaldehyde
• CAS: 109838-82-6；110289-01-5；114376-80-6；120852-20-2
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: JYJUDDQCGHNPBK-MNOVXSKESA-N

物化性质

• 沸点：
  380.6±42.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-(4R^*,5R^*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one 在 二甲基亚砜 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 (+/-)-(4R^*,5R^*)-5-benzoyl-1-methyl-4-phenylpyrrolidin-2-one
  参考文献：
  名称：

  Diastereoselective and enantioselective total synthesis of the hepatoprotective agent clausenamide

  摘要：

  DOI：

  10.1021/jo00228a037
• 作为产物：
  描述：

  (+/-)-(4R^*,5R^*)-5-(hydroxymethyl)-1-methyl-4-phenylpyrrolidin-2-one 在 草酰氯 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 以75%的产率得到(+/-)-(4R^*,5R^*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one
  参考文献：
  名称：

  基于 Suzuki-Miyaura 偶联的 (+)-epi-Clausenamide 及其 3-脱氧类似物的对映异构体的对映选择性合成

  摘要：

  报道了两种具有生物学意义的黄皮酰胺类似物的首次对映选择性合成，即 (+)-epi-clausenamide 和 (-)-3-deoxy-epi-clausenamide。合成的关键步骤包括从 d - 和 l - 丝氨酸衍生物构建手性吡咯啉酮中间体，通过 Suzuki-Miyaura 偶联引入 C4-苯基以及通过苏式选择性格氏反应建立 C6 构型。详细描述了关键 Suzuki-Miyaura 偶联反应的优化。

  DOI：

  10.1055/s-0031-1290804

文献信息

• 4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17β-hydroxysteroid dehydrogenase. Part 3. Identification of lead candidate
  作者：Jill Wood、Cedo M. Bagi、Christiana Akuche、Antonietta Bacchiocchi、Jeremy Baryza、Marie-Luise Blue、Catherine Brennan、Ann-Marie Campbell、Soongyu Choi、James H. Cook、Patricia Conrad、Brian R. Dixon、Paul P. Ehrlich、Todd Gane、David Gunn、Ted Joe、Jeffrey S. Johnson、Jerold Jordan、Richard Kramss、Peiying Liu、Joan Levy、Derek B. Lowe、Ian McAlexander、Reina Natero、Anikó M. Redman、William J. Scott、Christopher Town、Ming Wang、Yamin Wang、Zhonghua Zhang

  DOI：10.1016/j.bmcl.2006.06.041

  日期：2006.9

  A series of 4,5-disubstituted cis-pyrrolidinones was investigated as inhibitors of 17beta-HSD II for the treatment of osteoporosis. Biochemical data for several compounds are given. Compound 42 was selected as the lead candidate.

  研究了一系列4,5-二取代的顺式-吡咯烷酮作为17β-HSDII抑制剂，用于治疗骨质疏松症。给出了几种化合物的生化数据。选择化合物42作为主要候选化合物。
• 17-Beta-hydroxysteroid dehydrogenase-II inhibitors
  申请人：——

  公开号：US20030087952A1

  公开（公告）日：2003-05-08

  17-beta-hydroxysteroid dehydrogenase-I1 inhibitors having the structural formula 1 wherein the phenyl group labeled A and the group —C(R 4 )(R 6 )Y are oriented cis to each other; W represents 0 or S; R 1 represents —H or optionally substituted —(C 1 -C 4 )alkyl; n represents 0 or an integer of 1-3; and R 2 represents any of a variety of substituents on ring A. R 4 generally represents —H but may be a bond terminating at the ortho position of ring A. Y represents fluorine, —OR 5 , or —SR 5 , and R 5 represents —H. optionally substituted —(C 1 -C 4 )alkyl, optionally substituted -phenyl, optionally substituted —(C 1 -C 4 )alkyl-phenyl, or optionally substituted —(C 1 -C 4 )acyl. R 6 represents any of a variety of groups as defined in the specification and claims, including heteroaryl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, alkynyl, arylalkynyl, heteroarylalkynyl, aryl, and indolyl. Pharmaceutically acceptable salts and N-oxides of these materials are also included. Also claimed are pharmaceutical compositions containing these materials and methods of using them.

  17-beta-羟基类固醇脱氢酶I1抑制剂具有结构式1，其中苯基A和基团—C(R4)(R6)Y相对取向；W代表0或S；R1代表—H或可选择取代的—(C1-C4)烷基；n代表0或1-3的整数；R2代表环A上的各种取代基之一。R4通常代表—H，但可能是终止在环A的邻位的键。Y代表氟、—OR5或—SR5，R5代表—H、可选择取代的—(C1-C4)烷基、可选择取代的苯基、可选择取代的—(C1-C4)烷基-苯基或可选择取代的—(C1-C4)酰基。R6代表根据说明书和索赔中定义的各种基团之一，包括杂芳基、芳基烷基、杂芳基烷基、芳基烯基、杂芳基烯基、炔基、芳基炔基、杂芳基炔基、芳基和吲哚基。还包括这些物质的药用合适盐和N-氧化物。还声明包含这些物质的药物组合物和使用它们的方法。
• Formal Synthesis of (±)-Clausenamide by NHC-Catalyzed γ-Lactam Formation
  作者：Jeffrey W. Bode、Ming He、Michael Rommel

  DOI：10.3987/com-12-s(n)128

  日期：——

  (+/-)-Clausenamide is a biologically active gamma-lactam isolated as a racemic mixture from Clausena lansium. Reported medicinal properties include hepatoprotective effects as well as neuroprotective and nootropic activity. In order to improve synthetic access to this molecule and its analogues, and to devise a route amenable to asymmetric catalysis, we have developed a new formal synthesis of (+/-)-clausenamide based on an N-heterocyclic carbene (NHC) catalyzed annulation of cinnamaldehyde and an unsaturated imine. The key gamma-lactam forming annulation proceeds at room temperature in good yield and excellent diastereoselectivity. Preliminary efforts towards an enantioselective variant are also reported.

  (±)-Clausenamide是一种具有生物活性的γ-内酰胺，作为消旋混合物从Clausena lansium中分离得到。据报道，它具有保肝作用以及神经营养和促智活性。为了提高合成通向该分子及其类似物的可进入性，并设计一条适用于不对称催化的路线，我们开发了一种新的(±)-clausenamide的正式合成方法，基于N-杂环卡宾（NHC）催化的肉桂醛和不饱和亚胺的环化反应。关键的γ-内酰胺形成环化反应在室温下以良好产率和出色的非对映选择性进行。初步努力实现对映选择性变体的结果也已报告。
• 17-beta-hydroxysteroid dehydrogenase-II inhibitors
  申请人：Bayer Pharmaceuticals Corporation

  公开号：US06784167B2

  公开（公告）日：2004-08-31

  17-beta-hydroxysteroid dehydrogenase-II inhibitors having the structural formula wherein the phenyl group labeled A and the group —C(R4)(R6)Y are oriented cis to each other; W represents O or S; R1 represents —H or optionally substituted —(C1-C4)alkyl; n represents 0 or an integer of 1-3; and R2 represents any of a variety of substituents on ring A. R4 generally represents —H but may be a bond terminating at the ortho position of ring A. Y represents fluorine, —OR5, or —SR5, and R5 represents —H, optionally substituted —(C1-C4)alkyl, optionally substituted -phenyl, optionally substituted —(C1-C4)alkyl-phenyl, or optionally substituted —(C1-C4)acyl. R6 represents any of a variety of groups as defined in the specification and claims, including heteroaryl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, alkynyl, arylalkynyl, heteroarylalkynyl, aryl, and indolyl. Pharmaceutically acceptable salts and N-oxides of these materials are also included. Also claimed are pharmaceutical compositions containing these materials and methods of using them.

  具有以下结构式的17-beta-羟基类固醇脱氢酶-II抑制剂，其中标记为A的苯基和群体—C（R4）（R6）Y定向为顺式构型；W代表O或S；R1代表—H或可选取代的—（C1-C4）烷基；n代表0或1-3的整数；R2代表环A上的各种取代基。R4通常代表—H，但可能是终止于环A的邻位的键。Y代表氟，—OR5或—SR5，R5代表—H，可选取代的—（C1-C4）烷基，可选取代的苯基，可选取代的—（C1-C4）烷基-苯基或可选取代的—（C1-C4）酰基。R6代表规范和权利要求中定义的各种群体，包括杂环芳基，芳基烷基，杂环芳基烷基，芳基烯基，杂环芳基烯基，炔基，芳基炔基，杂环芳基炔基，芳基和吲哚基。还包括这些材料的药学上可接受的盐和N-氧化物。还声明了含有这些材料的制药组合物和使用它们的方法。
• 5-Phenyl-1,2,3a,4,5,9b-hexahydro-3H-benz [e] indole, ihre Herstellung und Berwendung als Arzneimittel
  申请人：BASF Aktiengesellschaft

  公开号：EP0292819A2

  公开（公告）日：1988-11-30

  Es werden 5-Phenyl-1,2,3a,4,5,9b-hexahydro-3H-benz[e]indole der Formel in der R¹ - R⁵ die in der Beschreibung angegebene Bedeutung besitzen, sowie deren Herstellung beschrieben. Die Substanzen eignen sich zur Bekämpfung von Krankheiten.

  5-苯基-1,2,3a,4,5,9b-六氢-3H-苯并[e]吲哚，其式为 式中 R¹ - R⁵ 的含义及其制备方法。这些物质适用于防治疾病。