(S)-2-(3-bromo-4-hydroxyphenyl)-2-((tert-butoxycarbonyl)amino)acetic acid | 1213399-90-6

• 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
• 英文名称: (S)-2-(3-bromo-4-hydroxyphenyl)-2-((tert-butoxycarbonyl)amino)acetic acid
• 英文别名: (2S)-2-(3-bromo-4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid
• CAS: 1213399-90-6
• 化学式: C₁₃H₁₆BrNO₅
• 分子量: 346.178
• InChiKey: UYHAGBGUYCTQPD-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-(3-bromo-4-hydroxyphenyl)-2-((tert-butoxycarbonyl)amino)acetic acid 在 吗啉 、 咪唑 、 四(三苯基膦)钯 、 silver benzoate 、 氯甲酸乙酯 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.33h， 生成 N-tert-butoxycarbonyl-(R)-3-bromo-4-(tert-butyldimethylsilyloxy)-β-phenylalanine-{allyl [(E)-4-methylhept-4-enoate]-7-yl} ester
  参考文献：
  名称：

  具有强细胞抑制特性的简化卤化软骨酰胺衍生物的合成

  摘要：

  从软骨酰胺的 ω-羟基酸中去除甲基和立体中心会导致这些有趣的缩肽的细胞毒性显着下降。这种影响几乎可以通过在天然产物的 β-酪氨酸部分引入第二个氯原子来补偿。这些简化的软骨素比天然软骨素更容易获得。

  DOI：

  10.1002/ejoc.201403577
• 作为产物：
  描述：

  L-(+)-对羟基苯甘氨酸 在 氢溴酸 、 溴 、 溶剂黄146 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 40.0h， 生成 (S)-2-(3-bromo-4-hydroxyphenyl)-2-((tert-butoxycarbonyl)amino)acetic acid
  参考文献：
  名称：

  具有强细胞抑制特性的简化卤化软骨酰胺衍生物的合成

  摘要：

  从软骨酰胺的 ω-羟基酸中去除甲基和立体中心会导致这些有趣的缩肽的细胞毒性显着下降。这种影响几乎可以通过在天然产物的 β-酪氨酸部分引入第二个氯原子来补偿。这些简化的软骨素比天然软骨素更容易获得。

  DOI：

  10.1002/ejoc.201403577

文献信息

• NOVEL CHONDRAMIDE DERIVATIVES
  申请人：HELMOLTZ-ZENTRUM FÜR INFEKTIONSFORSCHUNG

  公开号：US20150291658A1

  公开（公告）日：2015-10-15

  The present invention provides novel chondramide derivatives of formula (I) which can be used for the treatment of cancer.

  本发明提供了一种新型的化学式（I）的骨软骨素衍生物，可用于治疗癌症。
• Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region
  作者：Anna K. Lampa、Sara M. Bergman、Sofia S. Gustafsson、Hiba Alogheli、Eva B. Åkerblom、Gunnar G. Lindeberg、Richard M. Svensson、Per Artursson、U. Helena Danielson、Anders Karlén、Anja Sandström

  DOI：10.1021/ml400217r

  日期：2014.3.13

  Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.
• One-Pot, Two-Step, Microwave-Assisted Palladium-Catalyzed Conversion of Aryl Alcohols to Aryl Fluorides via Aryl Nonaflates
  作者：Johan Wannberg、Charlotta Wallinder、Meltem Ünlüsoy、Christian Sköld、Mats Larhed

  DOI：10.1021/jo400255m

  日期：2013.4.19

  A convenient procedure for converting aryl alcohols to aryl fluorides via aryl nonafluorobutylsulfonates (ArONf) is presented. Moderate to good one-pot, two-step yields were achieved by this nonaflation and microwave-assisted, palladium-catalyzed fluorination sequence. The reductive elimination step was investigated by DFT calculations to compare fluorination with chlorination, proving a larger thermodynamic driving force for the aryl fluoride product. Finally, a key aryl fluoride intermediate for the synthesis of a potent HCV NS3 protease inhibitor was smoothly prepared with the novel protocol.
• Vinylated linear P2 pyrimidinyloxyphenylglycine based inhibitors of the HCV NS3/4A protease and corresponding macrocycles
  作者：Anna Lampa、Hiba Alogheli、Angelica E. Ehrenberg、Eva Åkerblom、Richard Svensson、Per Artursson、U. Helena Danielson、Anders Karlén、Anja Sandström

  DOI：10.1016/j.bmc.2014.10.010

  日期：2014.12

  With three recent market approvals and several inhibitors in advanced stages of development, the hepatitis C virus (HCV) NS3/4A protease represents a successful target for antiviral therapy against hepatitis C. As a consequence of dealing with viral diseases in general, there are concerns related to the emergence of drug resistant strains which calls for development of inhibitors with an alternative binding-mode than the existing highly optimized ones. We have previously reported on the use of phenylglycine as an alternative P2 residue in HCV NS3/4A protease inhibitors. Herein, we present the synthesis, structure-activity relationships and in vitro pharmacokinetic characterization of a diverse series of linear and macrocyclic P2 pyrimidinyloxyphenylglycine based inhibitors. With access to vinyl substituents in P3, P2 and P1' positions an initial probing of macrocyclization between different positions, using ring-closing metathesis (RCM) could be performed, after addressing some synthetic challenges. Biochemical results from the wild type enzyme and drug resistant variants (e.g., R155 K) indicate that P3-P1' macrocyclization, leaving the P2 substituent in a flexible mode, is a promising approach. Additionally, the study demonstrates that phenylglycine based inhibitors benefit from p-phenylpyrimidinyloxy and m-vinyl groups as well as from the combination with an aromatic P1 motif with alkenylic P1' elongations. In fact, linear P2-P1' spanning intermediate compounds based on these fragments were found to display promising inhibitory potencies and drug like properties. (C) 2014 Elsevier Ltd. All rights reserved.
• Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents
  作者：Anna Lampa、Angelica E. Ehrenberg、Sofia S. Gustafsson、Aparna Vema、Eva Åkerblom、Gunnar Lindeberg、Anders Karlén、U. Helena Danielson、Anja Sandström

  DOI：10.1016/j.bmc.2010.05.027

  日期：2010.7

  Phenylglycine has proved to be a useful P2 residue in HCV NS3 protease inhibitors. A novel pi-pi-interaction between the phenylglycine and the catalytic H57 residue of the protease is postulated. We hypothesized that the introduction of a vinyl on the phenylglycine might strengthen this pi-pi-interaction. Thus, herein is presented the synthesis and inhibitory potency of a series of acyclic vinylated phenylglycine-based HCV NS3 protease inhibitors. Surprisingly, inhibitors based on both D-and L-phenylglycine were found to be effective inhibitors, with a slight preference for the D-epimers. Furthermore, prime-side alkenylic extension of the C-terminal acylsulfonamide group gave significantly improved inhibitors with potencies in the nanomolar range (similar to 35 nM), potencies which were retained on mutant variants of the protease. (C) 2010 Elsevier Ltd. All rights reserved.