1-but-3-enyl-cyclopentanecarboxylic acid methyl ester | 220878-56-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 1-but-3-enyl-cyclopentanecarboxylic acid methyl ester
• 英文别名: 1-(3-Butenyl)Cyclopentane Carboxylic Acid Methyl Ester；methyl 1-but-3-enylcyclopentane-1-carboxylate
• CAS: 220878-56-8
• 化学式: C₁₁H₁₈O₂
• 分子量: 182.263
• InChiKey: GWQISQAMABBMHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-but-3-enyl-cyclopentanecarboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以55%的产率得到1-(3-Butenyl)cyclopentanecarboxylic acid
  参考文献：
  名称：

  吡咯烷和螺吡咯烷的不对称“环-环”合成

  摘要：

  据报道，在药物发现计划中，越来越重要的2,2-和3,3-二取代的吡咯烷和螺吡咯烷的不对称“夹子循环”合成已经得到发展。Cbz保护的双均烯丙基胺是通过烯烃易位反应将其“剪切”为硫代丙烯酸酯而活化的。通过手性磷酸催化的对映选择性分子内氮杂-Michael环化到活化的烯烃上，形成吡咯烷。反应进行了一系列取代，形成了具有高对映选择性的2，2-和3，3-二取代的吡咯烷和螺吡咯烷。通过与含酮和含氧酸酯的底物进行比较，证明了硫酯活化基团的重要性。DFT研究支持将aza-Michael环化作为决定速率和立体化学的步骤，并正确预测了主要对映异构体的形成。催化不对称合成具有“ DNA结合”和抗菌特性的N-甲基吡咯烷生物碱（R）-吡啶和（R）-bgugaine是使用“夹环”方法获得的。

  DOI：

  10.1021/acs.orglett.0c03090
• 作为产物：
  描述：

  4-碘-1-丁烯 、 环戊烷甲酸甲酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 1-but-3-enyl-cyclopentanecarboxylic acid methyl ester
  参考文献：
  名称：

  N-Cycloalkanoyl-l-Phenylalanine Derivatives as VCAM/VLA-4 Antagonists

  摘要：

  A systematic structure-activity relationship investigation of the lead compound I resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00386-4

文献信息

• N-alkanoylphenylalanine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06455550B1

  公开（公告）日：2002-09-24

  Compounds of the formula: are disclosed which have activity as inhibitors of binding between VCAM-1 and cells expressing VLA-4. Such compounds are useful for treating diseases whose symptoms and/or damage are related to the binding of VCAM-1 to cells expressing VLA-4.

  揭示了具有以下化学式的化合物，这些化合物具有作为VCAM-1和表达VLA-4的细胞之间结合抑制剂的活性。这些化合物对于治疗那些症状和/或损害与VCAM-1与表达VLA-4的细胞结合有关的疾病是有用的。
• [EN] SUBSTITUTED PHENYL CYCLOALKYL PYRROLIDINE (PIPERIDINE) SPIROLACTAMS AND AMIDES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] SPIROLACTAMES ET AMIDES DE PHÉNYLCYCLOALKYLPYRROLIDINE (PIPÉRIDINE) SUBSTITUÉS, LEUR PRÉPARATION ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI SA

  公开号：WO2011143150A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims respectively a series of substituted phenyl cycloalkyl pyrrolidine (piperidine) spirolactams and amides of formula (I) (Ia) and formula (Ib) as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted phenyl cycloalkyl pyrrolidine (piperidine) spirolactams and amides of formula (Ia) and (Ib), and intermediates therefor.

  本发明分别公开和声明了一系列取代苯基环烷基吡咯烷（哌啶）螺内酰胺和酰胺的化合物，其化学式如下（I）（Ia）和（Ib）。更具体地，本发明的化合物是H3受体调节剂，因此在治疗和/或预防包括与中枢神经系统相关的多种疾病在内的由H3受体调节的疾病中特别有用。此外，本发明还公开了取代苯基环烷基吡咯烷（哌啶）螺内酰胺和酰胺的制备方法，以及其中间体。
• [EN] SUBSTITUTED N-HETEROARYL SPIROLACTAM BIPYRROLIDINES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] BIPYRROLIDINES N-HÉTÉROARYL SPIROLACTAME SUBSTITUÉES, PROCÉDÉ DE PRÉPARATION ET USAGE THÉRAPEUTIQUE ASSOCIÉS
  申请人：SANOFI SA

  公开号：WO2011143148A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims a series of substituted N-heteroaryl spirolactam bipyrrolidines of formula ( Wherein R1, R2, Q1, Q2, Q3, Q4, X, m, n, p and s are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-heteroaryl spirolactam bipyrrolidines of formula (I) and intermediates therefor.

  本发明公开并声明了一系列式（其中R1、R2、Q1、Q2、Q3、Q4、X、m、n、p和s如本文所述。更具体地说，本发明的化合物是H3受体调节剂，因此在治疗和/或预防包括与中枢神经系统相关的疾病在内的多种受H3受体调节的疾病中有用作药用剂，此外，本发明还公开了制备式（I）的取代N-杂环烷基螺内酰胺双吡咯烷的方法及其中间体。
• [EN] SUBSTITUTED N-PHENYL SPIROLACTAM BIPYRROLIDINES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] BIPYRROLIDINES N-PHÉNYL SPIROLACTAME SUBSTITUÉES, PROCÉDÉ DE PRÉPARATION ET USAGE THÉRAPEUTIQUE ASSOCIÉS
  申请人：SANOFI SA

  公开号：WO2011143163A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims a series of substituted N-phenyl spirolactam bipyrrolidines of formula (I). (Formula (I)) Wherein R1, R2, R3, R4, m, n, p and s are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-phenyl spirolactam bipyrrolidines of formula (I) and intermediates therefor.

  本发明披露并声明了一系列代替N-苯基螺内酰胺双吡咯烷酮的化合物，其化学式为 (I)。其中，R1、R2、R3、R4、m、n、p 和 s 如本文所述。更具体地说，本发明的化合物是H3受体调节剂，因此在治疗和/或预防多种由H3受体调节的疾病中，尤其是与中枢神经系统相关的疾病中，可作为药用剂。此外，本发明还披露了制备化合物 (I) 的代替N-苯基螺内酰胺双吡咯烷酮以及其中间体的方法。
• Enantioselective “clip-cycle” synthesis of di-, tri- and spiro-substituted tetrahydropyrans
  作者：Khadra Alomari、N. Sai Pavan Chakravarthy、Bastien Duchadeau、Kristaps Ermanis、Paul A. Clarke

  DOI：10.1039/d2ob00023g

  日期：——

  ω-Unsaturated alcohols were “clipped” via alkene metathesis to a thioester activating group, which was followed by a chiral phosphoric acid catalyzed intramolecular oxa-Michael cyclization to yield tetrahydropyrans and spiro-tetrahydropyrans with excellent enantioselectivity. The mechanism and origin of the enantioselectivity was probed by DFT calculations and kinetic isotope studies, where there was

  ω-不饱和醇通过烯烃复分解被“剪裁”成硫酯活化基团，随后手性磷酸催化分子内氧杂-迈克尔环化产生具有优异对映选择性的四氢吡喃和螺-四氢吡喃。通过 DFT 计算和动力学同位素研究探讨了对映选择性的机制和起源，其中计算和合成研究之间存在极好的相关性。