(S)-氨基-(2-氟苯基)-乙酸 | 138751-04-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-氨基-(2-氟苯基)-乙酸
• 中文别名: 2-氟-L-苯甘氨酸；(S)-氨基-(2-氟-苯基)-乙酸
• 英文名称: (S)-2-amino-2-(2-fluorophenyl)acetic acid
• 英文别名: (S)-amino-(2-fluorophenyl)acetic acid；2-fluoro-L-α-phenylglycine；(+)-o-fluorophenylglycine；(2S)-2-azaniumyl-2-(2-fluorophenyl)acetate
• CAS: 138751-04-9
• 化学式: C₈H₈FNO₂
• 分子量: 169.155
• InChiKey: CGNMJIBUVDGMIY-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-氨基-(2-氟苯基)-乙酸 在 lithium aluminium tetrahydride 、 三乙酰氧基硼氢化钠 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 二乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 生成 (3S,6S)-6-(2-fluorophenyl)-3-isobutyl-piperazin-2-one
  参考文献：
  名称：

  Discovery of a Novel Class of Potent HCV NS4B Inhibitors: SAR Studies on Piperazinone Derivatives

  摘要：

  HTS screening identified compound 2a (piper-azinone derivative) as a low micromolar HCV genotype 1 (GT-1) inhibitor. Resistance mapping studies suggested that this piperazinone chemotype targets the HCV nonstructural protein NS4B. Extensive SAR studies were performed around 2a and the amide function and the C-3/C-6 cis stereochemistry of the piperazinone core were essential for HCV activity. A 10-fold increase in GT-1 potency was observed when the chiral phenylcyclopropyl amide side chain of 2a was replaced with p-fluorophenylisoxazole-carbonyl moiety (67). Replacing the C-6 nonpolar hydrophobic moiety of 67 with a phenyl moiety (95) did not diminish the GT-1 potency. A heterocyclic thiophene moiety (103) and an isoxazole moiety (108) were incorporated as isosteric replacements for the C-6 phenyl moiety (95), resulting in significant improvement in GT-1b and la potency. However, the piperazonone class of compounds lacks GT-2 activity and, consequently, were not pursued further into development.

  DOI：

  10.1021/jm4012643
• 作为产物：
  描述：

  2-氟-DL-Α-苯基甘氨酸 在 水 、 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 反应 3.0h， 生成 (S)-氨基-(2-氟苯基)-乙酸
  参考文献：
  名称：

  Soloshonok, V. A.; Galaev, I. Yu.; Shvyadas, V. K., Russian Journal of Bioorganic Chemistry, 1993, vol. 19, # 4, p. 228 - 232

  摘要：

  DOI：

文献信息

• Highly Enantioselective Titanium-Catalyzed Cyanation of Imines at Room Temperature
  作者：Abdul Majeed Seayad、Balamurugan Ramalingam、Kazuhiko Yoshinaga、Takushi Nagata、Christina L. L. Chai

  DOI：10.1021/ol902540h

  日期：2010.1.15

  A highly active and enantioselective titanium-catalyzed cyanation of imines at room temperature is described. The catalyst used is a partially hydrolyzed titanium alkoxide (PHTA) precatalyst together with a readily available N-salicyl-β-aminoalcohol ligand. Up to 98% ee was obtained with quantitative yields in 15 min of reaction time using 5 mol % of the catalyst. Various N-protecting groups such as

  描述了在室温下高活性和对映选择性的钛催化的亚胺氰化。所用的催化剂是部分水解的烷氧基钛（PHTA）预催化剂以及易于获得的N-水杨基-β-氨基醇配体。使用5 mol％的催化剂，在15分钟的反应时间内以定量收率获得了高达98％ee。可以耐受各种N保护基，例如苄基，苯甲基，Boc和PMP。
• Engineering of Hydroxymandelate Oxidase and Cascade Reactions for High-Yielding Conversion of Racemic Mandelic Acids to Phenylglyoxylic Acids and (<i>R</i>)- and (<i>S</i>)-Phenylglycines
  作者：Do-Yun Jung、Xirui Li、Zhi Li

  DOI：10.1021/acscatal.2c05596

  日期：2023.1.20

  purified enzymes (up to 93% yield and 426 mM) or Escherichia coli (HMC) cells expressing the three enzymes (up to 93% yield and 140 mM). The HMOTM-MR-KatE cascades were applied for the oxidation of seven other substituted MAs, producing the corresponding phenylglyoxylic acids with 90–99% conversions using purified enzymes or whole cells. Efficient conversion of racemic α-hydroxy acids to (S)- or (R)-α-amino

  通过羟基扁桃酸氧化酶 (HMO) 的定向进化，开发了一种醇氧化酶 (AOx)，用于将4-羟基扁桃酸 (4-HMA) (4-HMA) 对映选择性氧化为 4-羟基苯乙醛酸 (4-HPGA)，活性增强几轮迭代饱和诱变。工程改造的 HMO 突变体 A80G-T159S-T162Q (HMOTM) 催化 ( S )-4-HMA 氧化为 4-HPGA，催化效率 ( k cat / K M ) 提高了 23 倍。HMOTM 上的底物对接模拟表明 A80G 重新定向 FMN，而 T159S 和 T162Q 与底物的羧基形成氢键，从而促进底物结合和催化。(小号)-对映选择性 HMOTM 与扁桃酸消旋酶 (MR) 和过氧化氢酶 (KatE) 一起使用，以使用纯化的酶（高达 93% 的产率和 426 mM）或表达三种酶的大肠杆菌(HMC) 细胞（高达 93% 的产率和 140 mM）。HMOTM-MR-KatE
• Water soluble phosphines
  作者：David J Brauer、Stefan Schenk、Stefan Roßenbach、Michael Tepper、Othmar Stelzer、Thomas Häusler、William S Sheldrick

  DOI：10.1016/s0022-328x(99)00689-0

  日期：2000.3

  Nucleophilic phosphination of the potassium or sodium salt of the fluorophenylalanines (1a, 2a) or -glycines (3a, 4a) with potassium phosphides Ph(R)PK (R = Me, Ph) yields chiral phosphine ligands (1-7) with amino acid moieties, The X-ray structure of 3 . 2H(2)O (space group Pbca) has been determined showing a betaine type structure for the amino acid moiety. The alpha-methyl derivatives of the phosphinophenylglycines (10, 11) were obtained in an analogous manner as 1-7, ortho- and para-Fluoroacetophenones have been employed as starting material for the syntheses of alpha-[4-fluorophenyl]-alpha-methylglycine (9c) and its ortho-isomer (8c). the X-ray structure of its monohydrate has been determined (space group P (1) over bar). The N-acetyl (3b, 8e) and ester derivatives (3d, 8d) of 3 and 8c are accessible using standard procedures. Resolution of the diastereomeric salt 12 obtained from (S)-(+)-2-hydroxymethylpyrrolidine and racem-8e by fractionated crystallization yielded the (S,R)-isomer. The absolute configuration of(S,R)-12 was determined by X-ray structural analysis (space group P2(1)2(1)2(1)). Cleavage of (S,R)-12 with hydrochloric acid gave enantiopure (R)-8e [alpha](D)(20) = - 30.9 degrees (c = 1, CH3OH). (C) 2000 Elsevier Science S.A. All rights reserved.
• Discovery of a Novel Class of Potent HCV NS4B Inhibitors: SAR Studies on Piperazinone Derivatives
  作者：Ramesh Kakarla、Jian Liu、Devan Naduthambi、Wonsuk Chang、Ralph T. Mosley、Donghui Bao、Holly M. Micolochick Steuer、Meg Keilman、Shalini Bansal、Angela M. Lam、William Seibel、Sandra Neilson、Phillip A. Furman、Michael J. Sofia

  DOI：10.1021/jm4012643

  日期：2014.3.13

  HTS screening identified compound 2a (piper-azinone derivative) as a low micromolar HCV genotype 1 (GT-1) inhibitor. Resistance mapping studies suggested that this piperazinone chemotype targets the HCV nonstructural protein NS4B. Extensive SAR studies were performed around 2a and the amide function and the C-3/C-6 cis stereochemistry of the piperazinone core were essential for HCV activity. A 10-fold increase in GT-1 potency was observed when the chiral phenylcyclopropyl amide side chain of 2a was replaced with p-fluorophenylisoxazole-carbonyl moiety (67). Replacing the C-6 nonpolar hydrophobic moiety of 67 with a phenyl moiety (95) did not diminish the GT-1 potency. A heterocyclic thiophene moiety (103) and an isoxazole moiety (108) were incorporated as isosteric replacements for the C-6 phenyl moiety (95), resulting in significant improvement in GT-1b and la potency. However, the piperazonone class of compounds lacks GT-2 activity and, consequently, were not pursued further into development.
• Soloshonok, V. A.; Galaev, I. Yu.; Shvyadas, V. K., Russian Journal of Bioorganic Chemistry, 1993, vol. 19, # 4, p. 228 - 232
  作者：Soloshonok, V. A.、Galaev, I. Yu.、Shvyadas, V. K.、Kozlova, E. V.、Kotik, N. V.、et al.

  DOI：——

  日期：——