3-(4-fluorophenyl)glutaronitrile | 78533-75-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-fluorophenyl)glutaronitrile
• 英文别名: 3-(4-Fluorophenyl)pentanedinitrile
• CAS: 78533-75-2
• 化学式: C₁₁H₉FN₂
• 分子量: 188.204
• InChiKey: XHLODBNPRXHRSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  47.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)glutaronitrile 在 sodium hydroxide 、 双氧水 、 溴 、 sodium carbonate 作用下， 以 丙酮 为溶剂， 反应 17.5h， 生成 2-(4-fluorophenyl)propane-1,3-diamine
  参考文献：
  名称：

  Synthesis and antidepressant profiles of phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines

  摘要：

  A series of 4(6)- and 5-phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines were prepared and evaluated for central nervous system (CNS) effects in animal models. Several 5-phenyl-substituted compounds possessed potent antidepressant activity and all compounds in this series were devoid of significant activity in any of the other CNS (anticonvulsant, muscle relaxant, and depressant) assays. The most active compound in the in vivo screen for antidepressant activity (reversal of reserpine-induced hypothermia), 2-[(methoxycarbonyl)amino]-5-phenyl-1,4,5,6-tetrahydropyrimidine was considerably more potent than tricyclic antidepressant (TCA) standards. The 2-amino parent compound on the other hand was greater than 100-fold as effective as TCA's in in vitro inhibition of norepinephrine and dopamine uptake.

  DOI：

  10.1021/jm00383a002

文献信息

• Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen
  作者：YiTao Duan、PeiYuan Yao、Jie Ren、Chao Han、Qian Li、Jing Yuan、JinHui Feng、QiaQing Wu、DunMing Zhu

  DOI：10.1007/s11426-014-5139-2

  日期：2014.8

  prochiral 3-substituted glutaronitriles offers a new approach to access (S)-Pregabalin and (R)-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles (1a) or 3-(4′-chlorophenyl)glutaronitriles (1b) as the substrate. Some nitrilases were found to catalyze the desymmetric hydrolysis of 1a and 1b to form optically active 3-(cyanomethyl)-5-methylhexanoic acid (2a)

  前手性3-取代的戊二腈的去对称化提供了一种新的获取（S）-普瑞巴林和（R）-巴氯芬的方法。以3-异丁基戊二腈（1a）或3-（4'-氯苯基）戊二腈（1b）为底物，筛选了多种来源的腈水解酶。发现一些腈水解酶催化1a和1b的不对称水解，形成具有高对映异构体的光学活性3-（氰基甲基）-5-甲基己酸（2a）和3-（4'-氯苯基）-4-氰基丁酸（2b）。 excesse（EE）， 分别。使用传统的化学水解无法实现这一点。其中，AtNIT3生成（R）-2b，而BjNIT6402和HsNIT生成具有高转化率和ee值的相反的（S）-对映体。不仅腈水解酶对这些3-取代的戊二腈显示出不同的活性和立体选择性，底物的3-取代基对酶的活性和立体选择性也有很大的影响。（S）-2a和（S）-2b制备高产和ee分别使用BjNIT6402和HsNIT作为生物催化剂的数值。（的一个直接的Curtius重排小号- ）2A和（小号）
• Improving the catalytic efficiency and stereoselectivity of a nitrilase from <i>Synechocystis</i> sp. PCC6803 by semi-rational engineering en route to chiral γ-amino acids
  作者：Shanshan Yu、Peiyuan Yao、Jinlong Li、Jinhui Feng、Qiaqing Wu、Dunming Zhu

  DOI：10.1039/c8cy02455c

  日期：——

  3-substituted 4-cyanobutanoic acid offers an attractive approach to access chiral β-substituted γ-amino acids, an important moiety in pharmaceuticals. In this study, we employed enzyme-substrate docking and alanine scanning to determine the key amino acid residues which have a positive effect on the activity and stereoselectivity of a nitrilase from Synechocystis sp. PCC6803 (SsNIT). Then, site-saturation mutagenesis

  腈水解酶催化的3-取代的戊二腈脱对称为旋光的3-取代的4-氰基丁酸提供了一种吸引人的方法，可用于制备手性β-取代的γ-氨基酸，这是药物中的重要组成部分。在这项研究中，我们采用了酶-底物对接和丙氨酸扫描来确定关键氨基酸残基，这些残基对Synychocystis sp。的腈水解酶的活性和立体选择性具有积极的影响。PCC6803（不锈钢NIT）。然后，进行正氨基酸残基（H141，P194，M197，I201和F202）的位点饱和诱变和组合诱变，并用经鉴定，高活性和立体选择性可用于3-取代的戊二腈的脱对称化反应，以提供高达488 g L -1 d -1的高时空生产率的（S）-3-取代-4-氰基丁酸。分子计算表明，酶活性的提高可能是由于底物结合腔的扩大。有趣的是，同时提高了立体选择性。
• Inverting the Enantiopreference of Nitrilase‐Catalyzed Desymmetric Hydrolysis of Prochiral Dinitriles by Reshaping the Binding Pocket with a Mirror‐Image Strategy
  作者：Shanshan Yu、Jinlong Li、Peiyuan Yao、Jinhui Feng、Yunfeng Cui、Jianjiong Li、Xiangtao Liu、Qiaqing Wu、Jianping Lin、Dunming Zhu

  DOI：10.1002/anie.202012243

  日期：2021.2.15

  obtained. The mutant enzyme was applied in the preparation of optically pure (R)‐3‐isobutyl‐4‐cyanobutanoic acid ((R)‐2 a) and showed similar stereopreference inversion towards a series of 3‐substituted glutaronitriles. This study may offer a general strategy to switch the stereopreference of other nitrilases and other enzymes toward the desymmetric reactions of prochiral substrates with two identical

  应用镜像策略，即对底物结合袋进行对称分析，以鉴定两个关键的氨基酸残基W170和V198，这些残基可能会调节拟蓝藻中腈水解酶的对映体。PCC6803朝向3-异丁基戊二腈（1 a）。这两个残基的交换导致对映体优先转化（S，90％ee到R，47％ee）。通过常规位点饱和和组合诱变进一步重塑底物结合口袋，可以获得具有更高活性和立体选择性（99％ee，R）的变体E8。突变酶用于制备光学纯的（R）-3-异丁基-4-氰基丁酸（（R）-2 a），并显示出类似的立体偏爱，可逆于一系列3取代的戊二腈。这项研究可能提供一种一般策略，将其他腈水解酶和其他酶的立体偏好转换为具有两个相同反应性官能团的前手性底物的不对称反应。
• Microbial desymmetrization of 3-arylglutaronitriles, an unusual enhancement of enantioselectivity in the presence of additives
  作者：Mei-Xiang Wang、Chu-Sheng Liu、Ji-Sheng Li、Otto Meth-Cohn

  DOI：10.1016/s0040-4039(00)01518-5

  日期：2000.10

  3-arylglutaronitriles catalyzed by Rhodococcus sp. AJ270 cells proceeded regiospecifically and enantioselectively to produce S-(+)-3-aryl-4-cyanobutyric acids in high enantiomeric excess. Convenient chemoenzymatic syntheses of optically active R-(−)-4-amino-3-phenylbutyric acid and 4R-(−)-4-phenyltetrahydropyran-2-one are described.

  在有机添加剂（例如丙酮或β-环糊精）的存在下，或在己烷和磷酸盐缓冲液的双相系统中，红球菌（Rhodococcus sp。）催化3-芳基戊二腈的微生物脱对称化。AJ270细胞在区域特异性和对映体选择性上产生高对映体过量的S -（+）-3-芳基-4-氰基丁酸。描述了光学活性R -（-）-4-氨基-3-苯基丁酸和4 R -（-）-4-苯基四氢吡喃-2-酮的便捷化学酶促合成。
• 4-Phenyl and 5-phenyl-1,4,5,6-tetrahydropyrimidine derivatives, pharmaceutical compositions containing said derivatives, and process for preparing said derivatives
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0024776A1

  公开（公告）日：1981-03-11

  Compounds represented by the formula wherein A is H, where R is alkyl of one through six carbon atoms; X is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, alkoxy of one through four carbon atoms, benzyloxy, alkyl of one through four carbon atoms, alkylthio of one through four carbon atoms, alkylsulfinyl of one through four carbon atoms, alkylsulfonyl of one through four carbon atoms or trifluoromethyl; and Y is hydrogen or is the same as X; and R' is hydrogen or alkyl of one through four carbon atoms; the phenyl substituent carrying the X and Y is at the 4- or 5-position of the tetrahydropyrimidine ring when R' is hydrogen or is at the 5-position when R' is alkyl; and the pharmaceutically acceptable salts thereof. These compounds are pharmaceutically useful for treating depression, anxiety, convulsions, centrally-induced' skeletal muscle spasm and spasticity.

  由式表示的化合物 式中 A 是 H 其中 R 是一至六个碳原子的烷基； X 是氢、氟、氯、溴、碘、羟基、一至四个碳原子的烷氧基、苄氧基、一至四个碳原子的烷基、一至四个碳原子的烷硫基、一至四个碳原子的烷基亚磺酰基、一至四个碳原子的烷基磺酰基或三氟甲基；和 Y 是氢或与 X 相同；以及 R'为氢或一至四个碳原子的烷基；当 R' 为氢时，携带 X 和 Y 的苯基取代基位于四氢嘧啶环的 4 位或 5 位，当 R' 为烷基时，位于 5 位；及其药学上可接受的盐类。 这些化合物可用于治疗抑郁症、焦虑症、抽搐、中枢诱发的骨骼肌痉挛和痉挛。