2-methylpropoxycarbonyl (2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoate | 102988-95-4

• 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: 2-methylpropoxycarbonyl (2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 102988-95-4
• 化学式: C₂₂H₂₅NO₇
• 分子量: 415.443
• InChiKey: AWCIPDMCMYZGOB-IBGZPJMESA-N

物化性质

• 密度：
  1.245±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-methylpropoxycarbonyl (2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoate 在 盐酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 氯仿 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 7.5h， 生成 1-(N-benzyloxycarbonyl-L-tyrosyl)-2-methyl-2-chloroacetyl hydrazine
  参考文献：
  名称：

  Synthesis and inhibiting activities of 1-peptidyl-2-haloacetyl hydrazines toward cathepsin B and calpains

  摘要：

  Twenty-four 1-peptidyl-2-haloacetyl hydrazines which can be considered azapeptide halomethanes were synthesized and tested as models of cathepsin B, calpain I and calpain II inhibitors. Reagents designed for cathepsin B inactivation include Z-Tyr, Z-Tyr(I) and Z-Leu-Leu attached to an alpha-azaglycine or alpha-azaalanine unit in P1. By use of kinetic analysis, they proved to irreversibly inactivate cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate constants in the range 725-306 000 M-1s-1 were found for cathepsin B inactivation, with no more than 7 500 M-1s-1 for calpain II. K(I) for the reversible EI adducts ranged from 11 to 0.06 muM for cathepsin B. Structure of the possible reversible EI complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. I-Peptidyl-2-haloacetyl hydrazines designed for calpain inactivation include Boc-Val-(N(epsilon)-carbomethoxy)Lys-Leu, Boc-Val-Lys(N(epsilon)-Z)-Leu, Boc-Val-Lys(N(epsilon)-Tos)-Leu and Z-Leu-Leu attached to an alpha-azatyrosine unit in P1. They gave poor results. Title compounds proved to be selective for cysteine proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concentration. Relatively low aspecific alkylating properties were also demonstrated in tests using glutathione as the nucleophile.

  DOI：

  10.1016/0223-5234(93)90147-7
• 作为产物：
  描述：

  L-酪氨酸甲酯盐酸盐 在 N-甲基吗啉 、 sodium hydroxide 、 sodium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 氯仿 、 水 为溶剂， 反应 5.02h， 生成 2-methylpropoxycarbonyl (2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoate
  参考文献：
  名称：

  Enzyme-catalyzed irreversible formation of peptides containing D-amino acids

  摘要：

  DOI：

  10.1021/jo00364a021

文献信息

• New amino acid porphyrin derivatives. Part I: Synthesis
  作者：Martine Perrée-Fauvet、Catherine Verchère-Béaur、Eric Tarnaud、Gilles Anneheim-Herbelin、Nathalie Bône、Alain Gaudemer

  DOI：10.1016/0040-4020(96)00832-0

  日期：1996.10

  molecules that can bind to specific DNA-sequences, several new tri-(N-methyl-4-pyridiniumyl)porphyrins bearing an amino acid or peptide side-chain on the fourth meso aromatic substituent have been synthesized by efficient coupling of a monofunctionalized porphyrin with amino acids or peptides.

  为了获得可以与特定DNA序列结合的分子，已经通过有效偶联三氟甲磺酸，合成了几种新的在第四内消旋芳族取代基上带有氨基酸或肽侧链的三（N-甲基-4-吡啶基）卟啉。具有氨基酸或肽的单官能卟啉。
• Direct <i>N</i>-Glycan Profiling in the Presence of Tryptic Peptides on MALDI-TOF by Controlled Ion Enhancement and Suppression upon Glycan-Selective Derivatization
  作者：Yasuro Shinohara、Jun-ichi Furukawa、Kenichi Niikura、Nobuaki Miura、Shin-Ichiro Nishimura

  DOI：10.1021/ac0492766

  日期：2004.12.1

  Even though the formidably laborious and time-consuming nature of oligosaccharide analysis limits certain attempts to analyze the glycosylation profile, the significant elucidation of carbohydrate modifications is largely dependent on it. Aiming to substantially improve the sample preparation procedure, a novel protocol allowing glycan-specific detection in the presence of other species, such as tryptic peptides, on MALDI-TOF was proposed and then evaluated. The new protocol is based on the concept that the desorption/ionization efficiency of glycans could be selectively and substantially enhanced while drastically suppressing the other ion species upon glycan-selective derivatization. A series of known and novel labeling reagents, all of which carry hydrazide functionality to allow glycan-specific derivatization, were prepared and evaluated in terms of their abilities to enhance the detection sensitivity of glycans, suppress ions of other contaminants (e.g., peptides), and detect acidic oligosaccharides. Several novel reagents that possess hydrophobic residue(s) together with quaternary ammonium/pyridinium or guanidino functionalities significantly enhanced the detection sensitivity of oligosaccharides. When enzymatically deglycosylated tryptic ovalbumin digest was directly derivatized by these reagents and subjected to MALDI-TOF analysis without any prior purification, we observed that a single type of analyte ion (labeled glycan) could suppress a large majority of peptide ions while allowing a low-femtomole level detection of oligosaccharides. The efficacy of this approach was further evaluated using several other model glycoproteins, including α1-acid glycoprotein that contains a variety of sialylated oligosaccharides.

  尽管寡糖分析的艰巨性和耗时性限制了某些尝试来分析糖基化谱，但对碳水化合物修饰的显著阐明在很大程度上依赖于它。为了大幅度改善样品制备过程，提出并评估了一种新的方案，允许在存在其他物种（如胰蛋白酶肽）的情况下通过MALDI-TOF进行糖特定检测。新方案基于这样的概念：通过糖特定衍生化，可以有选择性地大幅度提高糖的解吸/电离效率，同时大幅度抑制其他离子物种。准备并评估了一系列已知和新颖的标记试剂，这些试剂都携带酰肼功能以便进行糖特定衍生化，根据它们提高糖检测灵敏度、抑制其他污染物离子（如肽）以及检测酸性寡糖的能力进行了评估。几种具有疏水残基和季铵/吡啶锪或胍基功能的新颖试剂显著提高了寡糖的检测灵敏度。当酶解脱糖基化的胰蛋白酶卵白蛋白消化物直接通过这些试剂衍生化，并在没有任何预先纯化的情况下进行MALDI-TOF分析时，我们观察到单一类型的分析离子（标记的糖）可以抑制大部分肽离子，同时允许低飞摩尔水平的寡糖检测。通过使用几种其他模型糖蛋白（包括含有各种唾液酸化寡糖的α1-酸性糖蛋白）进一步评估了这种方法的功效。
• Iodo and diiodotyrosine epoxysuccinyl derivatives as selective inhibitors of cathepsin B
  作者：C Giordano、R Calabretta、C Gallina、V Consalvi、R Scandurra、F Chiaia Noya、C Franchini

  DOI：10.1016/0223-5234(93)90046-h

  日期：1993.1

  Eight new analogs of L-trans-epoxysuccinyl-L-leucylamido(3-methyl)butane (E-64-c) containing Phe, Tyr, Tyr(I) or Tyr(I-2) in place of Leu, were synthesized and tested as inhibitors of papain, bovine spleen cathepsin B, calpain I and II from porcine red cells and porcine kidney, respectively. By use of kinetic methods, the new E-64 analogs proved to irreversibly inactivate both papain and cathepsin B via reversible enzyme-inhibitor intermediates EI. Second-order rate constants for inactivation were in the range 3500-55 100 M(-1)s(-1) for papain and 650-105 000 M(-1)s(-1) for cathepsin B. For the inactivation of calpain I and II they ranged between 250 and 2000 M(-1)s(-1) and were similar to those of the known E-64-c. The effectiveness of the amino acid contained in the inhibitors tested increased in the order Tyr(I) approximate to Tyr(I-2) < Tyr < Phe < Leu for papain and Phe < Tyr < Tyr(I)e Leu < Tyr(I-2) for cathepsin B inactivation. Replacement of the L with the D-trans-epoxysuccinyl unit caused a 10-100-fold decrease in inhibitor potencies.
• Peptidyl and azapeptidyl methylketones as substrate analog inhibitors of papain and cathepsin B
  作者：R Calabretta、C Giordano、C Gallina、V Morea、V Consalvi、R Scandurra

  DOI：10.1016/0223-5234(96)88312-7

  日期：1995.1

  Peptidyl methylketones containing Phe, Tyr, Tyr(I) Tyr(I-2), Leu and Ile in P-2 were synthesized and tested as substrate analog reversible inhibitors of papain and bovine spleen cathepsin B. The most effective cathepsin B inhibitor contained Tyr(I-2) and displayed an inhibition constant of 4.7 mu M at pH 6.8 and 25 degrees C, while Leu or lie gave practically inert analogs. Replacement of the amino acids in P-2 with the analogous alpha-azaamino acids, as well as the glycine in P-1 with alpha-azaglycine, led to complete loss of inhibiting activity. Introducing alkoxy substituents at the methyl adjacent to the ketone group generally resulted in more effective inhibitors, with inhibition constants in the micromolar range for both papain and cathepsin B.
• Frakefamide, an Analgesic Tetrapeptide:  Development of a Pilot-Plant-Scale Process
  作者：Henry M. Franzén、Galina Bessidskaia、Vahak Abedi、Anders Nilsson、Maths Nilsson、Lars Olsson

  DOI：10.1021/op020060k

  日期：2002.11.1

  A pilot-plant-process is described where frakefamide x HCl (L-tyrosyl-D-alanyl-p-fluoro-L-phenylalanyl-L-phenylalaninamide hydrochloride) was synthesised from its amino acid monomers in seven steps. The synthesis was performed in 70-L equipment, and the final product was obtained in 70% overall yield and in 99.5% purity. Only two intermediates were isolated, and the process required no chromatography. Peptide bond formation was promoted by isobutyl chloroformate-mediated mixed anhydride coupling reactions. The formed mixed anhydrides proved to be surprisingly stable, in most cases for several hours at -10 degreesC, and therefore suitable for large-scale peptide synthesis. Only traces, if any, of racemised coupling products were obtained. Benzyloxycarbonyl was used as amino protecting group throughout the synthesis, and its removal by hydrogenolysis proved to be fast and convenient on a large scale.