N-phenylacetyl-L-valine methyl ester | 1337550-75-0

• 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: N-phenylacetyl-L-valine methyl ester
• 英文别名: (2S)-3-methyl-2-(phenylacetylamino)butyric acid methyl ester；methyl (2S)-3-methyl-2-[(2-phenylacetyl)amino]butanoate
• CAS: 1337550-75-0
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: ZZNZSKXSTUYDIW-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-phenylacetyl-L-valine methyl ester 在 氧气 、 palladium diacetate 、 copper(II) bis(trifluoromethanesulfonate) 作用下， 以 2,2,2-三氟乙醇 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 以64%的产率得到(S)-2-(2-{2'-[((S)-1-methoxycarbonyl-2-methyl-propylcarbamoyl)methyl]biphenyl-2-yl}acetylamino)-3-methylbutyric acid methyl ester
  参考文献：
  名称：

  Oxidative C–H Homodimerization of Phenylacetamides

  摘要：

  A range of secondary and tertiary phenylacetamides undergo oxidative homodimerization to afford biaryls. The reaction proceeds under palladium catalysis in the presence of a copper cocatalyst and oxygen and is most effective for electron-rich substrates.

  DOI：

  10.1021/ol202212f
• 作为产物：
  描述：

  L-缬氨酸甲酯盐酸盐 、 苯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以84%的产率得到N-phenylacetyl-L-valine methyl ester
  参考文献：
  名称：

  Oxidative C–H Homodimerization of Phenylacetamides

  摘要：

  A range of secondary and tertiary phenylacetamides undergo oxidative homodimerization to afford biaryls. The reaction proceeds under palladium catalysis in the presence of a copper cocatalyst and oxygen and is most effective for electron-rich substrates.

  DOI：

  10.1021/ol202212f

文献信息

• Direct Amidation of Amino Acid Derivatives Catalyzed by Arylboronic Acids: Applications in Dipeptide Synthesis
  作者：Shouxin Liu、Yihua Yang、Xinwei Liu、Farhana K. Ferdousi、Andrei S. Batsanov、Andrew Whiting

  DOI：10.1002/ejoc.201300560

  日期：2013.9

  The direct amidation of amino acid derivatives catalyzed by arylboronic acids has been examined. The reaction was generally slow relative to simple amine-carboxylic acid combinations though proceeded at 65–68 °C generally avoiding racemization. 3,4,5-Trifluorophenylboronic and o-nitrophenylboronic acids were found to be the best catalysts, though for slower dipeptide formations, high catalyst loadings

  已经研究了由芳基硼酸催化的氨基酸衍生物的直接酰胺化。相对于简单的胺-羧酸组合，该反应通常较慢，但通常在 65-68°C 下进行，避免了外消旋化。发现 3,4,5-三氟苯基硼酸和邻硝基苯基硼酸是最好的催化剂，但对于较慢的二肽形成，需要高催化剂负载量，并且发现了两种芳基硼酸之间有趣的协同催化作用。
• Direct amide formation from unactivated carboxylic acids and amines
  作者：C. Liana Allen、A. Rosie Chhatwal、Jonathan M. J. Williams

  DOI：10.1039/c1cc15210f

  日期：——

  The direct coupling of unactivated carboxylic acids with amines can be performed in toluene 110 degrees C in the absence of catalyst. The use of simple zirconium catalysts at 5 mol% loading gave amide formation in as little as 4 h.

  未活化的羧酸与胺的直接偶联可以在不存在催化剂的情况下在甲苯110℃下进行。使用简单的锆催化剂（负载量为5 mol％）可在短短4小时内形成酰胺。
• Lipophilic Permeability Efficiency Reconciles the Opposing Roles of Lipophilicity in Membrane Permeability and Aqueous Solubility
  作者：Matthew R. Naylor、Andrew M. Ly、Mason J. Handford、Daniel P. Ramos、Cameron R. Pye、Akihiro Furukawa、Victoria G. Klein、Ryan P. Noland、Quinn Edmondson、Alexandra C. Turmon、William M. Hewitt、Joshua Schwochert、Chad E. Townsend、Colin N. Kelly、Maria-Jesus Blanco、R. Scott Lokey

  DOI：10.1021/acs.jmedchem.8b01259

  日期：2018.12.27

  As drug discovery moves increasingly toward previously "undruggable" targets such as protein-protein interactions, lead compounds are becoming larger and more lipophilic. Although increasing lipophilicity can improve membrane permeability, it can also incur serious liabilities, including poor water solubility, increased toxicity, and faster metabolic clearance. Here we introduce a new efficiency metric, especially relevant to "beyond rule of 5" molecules, that captures, in a simple, unitless value, these opposing effects of lipophilicity on molecular properties. Lipophilic permeability efficiency (LPE) is defined as log D-dec/w(7.4) - m(lipo)cLogP + b(scaffold), where log D-dec/w(7.4) is the experimental decadiene-water distribution coefficient (pH 7.4), cLogP is the calculated octanol-water partition coefficient, and m(lipo) and b(scaffold) are scaling factors to standardize LPE values across different cLogP metrics and scaffolds. Using a variety of peptidic and nonpeptidic macrocycle drugs, we show that LPE provides a functional assessment of the efficiency with which a compound achieves passive membrane permeability at a given lipophilicity.