(2-naphthalenylmethyl)-(2-propynyl)propanedioic acid diethyl ester | 288632-82-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (2-naphthalenylmethyl)-(2-propynyl)propanedioic acid diethyl ester
• 英文别名: 2-naphthalen-2-ylmethyl-2-propargylmalonic acid diethyl ester；Diethyl 2-(naphthalen-2-ylmethyl)-2-prop-2-ynylpropanedioate
• CAS: 288632-82-6
• 化学式: C₂₁H₂₂O₄
• 分子量: 338.403
• InChiKey: GEGWJIFEZRFYFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-naphthalenylmethyl)-(2-propynyl)propanedioic acid diethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 2-naphthalen-2-ylmethyl-4-pentynoic acid
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Haloenol Lactones:  Site-Directed and Isozyme-Selective Glutathione S-Transferase Inhibitors

  摘要：

  Overexpression of glutathione S-transferase (GST), particularly the GST-pi isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-pi inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-pi, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-pi inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-pi was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-pi with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.

  DOI：

  10.1021/jm0499615
• 作为产物：
  描述：

  2-萘甲醇 在 4-二甲氨基吡啶 、 sodium ethanolate 、 三乙胺 、 对甲苯磺酰氯 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 (2-naphthalenylmethyl)-(2-propynyl)propanedioic acid diethyl ester
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Haloenol Lactones:  Site-Directed and Isozyme-Selective Glutathione S-Transferase Inhibitors

  摘要：

  Overexpression of glutathione S-transferase (GST), particularly the GST-pi isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-pi inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-pi, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-pi inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-pi was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-pi with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.

  DOI：

  10.1021/jm0499615

文献信息

• A Gallium-Catalyzed Cycloisomerization/Friedel−Crafts Tandem
  作者：Hui-Jing Li、Régis Guillot、Vincent Gandon

  DOI：10.1021/jo101709n

  日期：2010.12.17

  specificity of gallium has been exploited for the synthesis of valuable polycyclic compounds that would be very difficult to prepare otherwise. For instance, tetrahydroisoquinolines and tetrahydrobenzoazepines have been obtained by selective 6-exo-dig or 7-endo-dig cyclization of N-tethered 1,6-arenynes. DFT calculations were carried out to shed light on the mechanism and provide a rationale for this regiodivergency

  在贵金属（Au，Pt，Ru）和第13组（Ga，In）金属催化下，1,6-芳烃重排以高产率，区域控制的方式生成1,2-二氢萘。当反应在富电子芳烃（苯甲醚，苯酚，吲哚衍生物）存在下进行时，可在环异构化步骤之后添加Friedel-Crafts。事实证明只有GaX 3盐能够催化这两个C键形成事件。镓的这种特异性已被用于合成有价值的多环化合物，否则该化合物将很难制备。例如，四氢异喹啉和四氢苯并a庚因已通过选择性6- exo- dig或7- endo获得-N-连接的1，6-芳烃的-dig环化。进行了DFT计算以阐明其机理，并为这种区域差异提供了理论依据。计算还揭示了系链在碳正离子物种稳定中的基本作用。镓和金催化的级联反应中其他类型底物的差异反应性也被暴露出来，表明这两种方法是互补的。特别地，在镓催化下促进了双分子Friedel-Crafts的添加。
• Ru(II)- and Pt(II)-Catalyzed Cycloisomerization of ω-Aryl-1-alkynes. Generation of Carbocationic Species from Alkynes and Transition Metal Halides and Its Interception by an Aromatic Ring
  作者：Naoto Chatani、Hiroki Inoue、Tsutomu Ikeda、Shinji Murai

  DOI：10.1021/jo000255v

  日期：2000.8.1

  the cyclization mode is dependent on the length of the tethers. The reaction is limited to substrates containing terminal alkynes. A key step of the reaction is the intramolecular interception by an aromatic ring of the vinylmetal complex 2, which contains a cation center at the beta-position, generated from the electrophilic addition of transition metal halides toward an alkyne. The more electron-rich

  用催化量的过渡金属氯化物如PtCl（2）处理芳基-1-炔烃，例如4-芳基-1-丁炔，5-芳基-1-戊炔和6-芳基-1-己炔和[RuCl（2）（CO）（3）]（2），在80°C的甲苯中进行环异构化，生成二氢萘或二氢苯并环庚烯，其中环化方式取决于系链的长度。该反应限于含有末端炔烃的底物。该反应的关键步骤是乙烯基金属配合物2的芳香环在分子内的拦截，该芳香环在β位置包含一个阳离子中心，这是由过渡金属卤化物向炔烃的亲电加成而产生的。较富电子的芳基体系更具反应性。
• Cycloisomerization of ω-Aryl-1-alkynes:  GaCl₃ as a Highly Electrophilic Catalyst for Alkyne Activation
  作者：Hiroki Inoue、Naoto Chatani、Shinji Murai

  DOI：10.1021/jo016232d

  日期：2002.2.1

  Cycloisomerization of a variety of omega-aryl-1-alkynes, where omega = 5 or 6, in the presence of a catalytic amount of GaCl3 provided dihydronaphthalene derivatives or dihydrobenzocycloheptenes, respectively, in high yields.