(S)-[5-[(叔丁氧羰基)氨基]-6-[(4-硝基苯基)氨基]-6-氧代己基]氨基甲酸苯甲酯 | 51078-31-0

• 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
• 中文名称: (S)-[5-[(叔丁氧羰基)氨基]-6-[(4-硝基苯基)氨基]-6-氧代己基]氨基甲酸苯甲酯
• 中文别名: BOC-Z-L-赖氨酸对硝基苯酰胺
• 英文名称: Boc-L-Lys(Z)-pNA
• 英文别名: Boc-lys(Z)-pna；benzyl N-[(5S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-(4-nitroanilino)-6-oxohexyl]carbamate
• CAS: 51078-31-0
• 化学式: C₂₅H₃₂N₄O₇
• 分子量: 500.552
• InChiKey: SPLJZTUHLDXXAK-NRFANRHFSA-N

物化性质

• 沸点：
  739.1±60.0 °C(Predicted)
• 密度：
  1.246
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (S)-[5-[(叔丁氧羰基)氨基]-6-[(4-硝基苯基)氨基]-6-氧代己基]氨基甲酸苯甲酯 在 N-乙基吗啉 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 N-Z-D-valyl-leucyl-N^ε-Z-lysine p-nitroanilide
  参考文献：
  名称：

  Martynov, V. F.; Pozdnev, V. F.; Smirnov, A. O., Journal of general chemistry of the USSR, 1990, vol. 60, # 2.2, p. 391 - 395

  摘要：

  DOI：
• 作为产物：
  描述：

  N-Boc-N'-Cbz-L-赖氨酸 、 N,N'-bis(4-nitrophenyl)phospheneimidous amide 在 吡啶 作用下， 反应 2.0h， 以60%的产率得到(S)-[5-[(叔丁氧羰基)氨基]-6-[(4-硝基苯基)氨基]-6-氧代己基]氨基甲酸苯甲酯
  参考文献：
  名称：

  Reinvestigation of the Phosphazo Method and Synthesis ofN-(t-Butoxycarbonyl)-L-argininep-Nitroanilide and a Chromogenic Enzyme Substrate for the Factor Xa

  摘要：

  为将磷氮法应用于合成对硝基苯胺(pNA)的叔丁氧羰基(Boc)和苄氧羰基(Z)氨基酸，重新研究了反应条件。

  DOI：

  10.1246/bcsj.64.1422

文献信息

• A convenient synthesis of amino acid p-nitroanilides; synthons in the synthesis of protease substrates
  作者：Dirk T.S. Rijkers、Hans P.H.M. Adams、H. Coenraad Hemker、Godefridus I. Tesser

  DOI：10.1016/0040-4020(95)00671-t

  日期：1995.10

  A method is described for the synthesis of Nα-protected bi- and trifunctional amino acid p-nitroanilides. The reaction uses phosphorus oxychloride as the condensing agent. The synthesis is simple, rapid, free of racemization and affords yields between 70–90%. The synthesis can be performed not only with amino acid derivatives of the urethane type including acid-labile (Z. Boc) and base-labile (Fmoc

  一种方法是为N的合成所述α -保护的二-和三官能氨基酸p -nitroanilides。该反应使用三氯氧化磷作为缩合剂。合成简单，快速，没有消旋作用，收率在70-90％之间。可以进行合成不仅与聚氨酯类的氨基酸衍生物，包括酸不稳定（Z. Boc）和碱不稳定的羰基（Fmoc，MSC）N α -proteclivc功能或烯丙基衍生的保护，而且还用N α -三烯丙基氨基酸，尽管收率较低。该反应在吡啶中进行，其机理暗示了通过与二氯二磷酸（HOPOCl 2）形成混合酸酐来进行羧基活化。
• New methods and reagents in organic synthesis. 69. A new synthesis of .ALPHA.-amino acid and peptide amides of aromatic amines using a modified Curtius reaction with diphenyl phosphorazidate.
  作者：TAKAYUKI SHIOIRI、MITSUO MURATA、YASUMASA HAMADA

  DOI：10.1248/cpb.35.2698

  日期：——

  As a basic study on the efficient synthesis of chromogenic and fluorogenic peptidase substrates, we investigated possible general methods for the synthesis of α-amino acid and peptide amides of aromatic amines. Preparation of Boc-L-Leu-pNA (1) as a model compound was attempted by (1) the coupling of Boc-L-Leu-OH with p-nitroaniline, (2) the reaction of Boc-L-Leu OH with p-nitrophenyl isocyanate, and (3) the reaction of Boc-L-Leu-OH with the product formed from p-nitrobenzoic acid through the modified Curtius reaction with diphenyl phosphorazidate ((C6H5O) 2P (O) N3) in a one-pot process. The third method was found to be a general and efficient method for the preparation of α-amino acid amides of aromatic amines. Application of this method to the preparation of a peptidase substrate, Bz-L-Ile-L-Glu (OMe) -Gly-L-Arg-pNA (2), has also been successfully achieved.

  作为染料和荧光素酶底物高效合成的基础研究，我们探索了合成芳香胺类α-氨基酸和肽酰胺的可能通用方法。通过以下三种方法尝试制备模型化合物Boc-L-Leu-pNA (1)：(1) Boc-L-Leu-OH与对硝基苯胺的偶联反应，(2) Boc-L-Leu-OH与对硝基苯基异氰酸酯的反应，以及(3) 在一步法中将Boc-L-Leu-OH与通过二苯基磷酰叠氮((C6H5O) 2P (O) N3)改进的Curtius反应生成的对硝基苯甲酸产物反应。发现第三种方法是制备芳香胺类α-氨基酸酰胺的一种通用且高效的方法。这种方法也已成功应用于制备肽酶底物Bz-L-Ile-L-Glu (OMe) -Gly-L-Arg-pNA (2)。
• Development of Active Center-Directed Inhibitors against Plasmin.
  作者：Naoki TENO、Keiko WANAKA、Yoshio OKADA、Yuko TSUDA、Utako OKAMOTO、Akiko HIJIKATA-OKUNOMIYA、Taketoshi NAITO、Shosuke OKAMOTO

  DOI：10.1248/cpb.39.2340

  日期：——

  Active center-directed inhibitors of plasmin were designed based on the structure of specific substrates of plasmin and then synthesized. Their effects on plasmin were examined and the structure-inhibitory activity relationship was studied. Nα-trans-4-Aminomethylcyclohexanecarbonyllysine 4-benzoylanilide (Tra-Lys-BZA) inhibited plasmin activities toward S-2251 and fibrin with IC50 values of 15 and 6.1 μM, respectively and Nα-trans-4-aminomethylcyclohexanecarbonyllysine 4-benzylpiperidine amide (Tra-Lys-BPP) did not show any detectable inhibitory activity. Moreover, it was revealed that Tra-Lys-4-methoxycarbonylanilide inhibited plasma kallikrein more potently than plasmin.

  基于纤溶酶的特定底物结构设计了活性中心导向的纤溶酶抑制剂，并进行了合成。研究了它们对纤溶酶的效应以及结构-抑制活性的关系。Nα-反式-4-氨甲基环己烷羰基赖氨酸4-苯甲酰苯胺（Tra-Lys-BZA）对S-2251和纤维蛋白的IC50值分别为15和6.1μM，而Nα-反式-4-氨甲基环己烷羰基赖氨酸4-苄基哌啶酰胺（Tra-Lys-BPP）则没有显示出任何可检测的抑制活性。此外，研究发现Tra-Lys-4-甲氧羰基苯胺对血浆激肽释放酶的抑制作用比纤溶酶更强。
• Synthesis of chromogenic substrates specific for human spleen fibrinolytic proteinase (SFP) and human leukocyte elastase (LE).
  作者：YOSHIO OKADA、YUKO TSUDA、AKIO HIRATA、YOKO NAGAMATSU、UTAKO OKAMOTO

  DOI：10.1248/cpb.30.4060

  日期：——

  Various peptide anilides were synthesized by a conventional method with the object of obtaining specific substrates for human spleen fibrinolytic proteinase (SFP) and human leukocyte elastase (LE) in order to compare the substrate specificity of SFP with that of LE. It was found that the P1 Val compound among succinyl tripeptide p-nitroanilides (Suc-Tyr-Leu-X-pNA) exhibited the highest kcat/Km values for hydrolysis by SFP and LE, however, the tetrapeptide Suc-Ala-Tyr-Leu-Val-pNA [kcat/Km values (M-1S-1) for hydrolysis by SFP and LE : 84000 and 48000, respectively] was the preferred chromogenic substrate for SFP and LE because of its high solubility in the buffer and its moderate kcat/Km values. The substrate specificity of SFP was found to be similar to that of LE.

  通过常规方法合成了多种肽苯胺，目的是获得人类脾纤维蛋白溶解酶（SFP）和人类白细胞弹性蛋白酶（LE）的特定底物，以便比较SFP和LE的底物特异性。研究发现，琥珀酰三肽对硝基苯胺（Suc-Tyr-Leu-X-pNA）中的P1 Val化合物在SFP和LE的水解反应中表现出最高的kcat/Km值，然而，四肽Suc-Ala-Tyr-Leu-Val-pNA（SFP和LE的水解反应的kcat/Km值（M-1S-1）：分别为84000和48000）是SFP和LE的首选显色底物，因为它具有在缓冲液中的高溶解性和适中的kcat/Km值。发现SFP的底物特异性与LE的相似。
• OYAMADA, HIDEKAZU;SAITO, TAKASHI;INABA, SHINSAKU;UEKI, MASAAKI, BULL. CHEM. SOC. JAP., 64,(1991) N, C. 1422-1424
  作者：OYAMADA, HIDEKAZU、SAITO, TAKASHI、INABA, SHINSAKU、UEKI, MASAAKI

  DOI：——

  日期：——