benzyl N-tert-butyloxycarbonyl-L-γ-glutamate α-N-methylamide | 56698-52-3

• 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: benzyl N-tert-butyloxycarbonyl-L-γ-glutamate α-N-methylamide
• 英文别名: N-(tert-butoxycarbonyl)-L-glutamic acid 1-methylamide 5-benzyl ester；benzyl (4S)-5-(methylamino)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate
• CAS: 56698-52-3
• 化学式: C₁₈H₂₆N₂O₅
• 分子量: 350.415
• InChiKey: RBXSJPUNZFWNAW-AWEZNQCLSA-N

物化性质

• 熔点：
  127-128 °C
• 沸点：
  551.0±50.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl N-tert-butyloxycarbonyl-L-γ-glutamate α-N-methylamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 Leu-Ser-p-nitro-Phe-Nle-Ala-Leu-OMe*TFA
  参考文献：
  名称：

  Fucose derivatives, drugs containing the same as active ingredient, and

  摘要：

  化合物的公式（I）：##STR1##其中X.sup.1是以下公式之一的基团（1）、（2）和（3）：##STR2##R.sup.1是支链长链烷基基团，R.sup.2是--CONHR.sup.3、羧基或氢原子，n是0、1或2的整数，R.sup.3是较低的烷基基团或苯基，或其药学上可接受的盐，用作选择素抑制剂，可用于预防或治疗各种炎症性疾病，如炎症性皮炎（例如特应性皮炎、接触性过敏、光敏性皮炎等）、自身免疫慢性疾病（例如类风湿关节炎、慢性甲状腺炎等）和缺血再灌注损伤。

  公开号：

  US05919769A1
• 作为产物：
  描述：

  N-叔丁氧羰基-L-谷氨酸 5-苄酯 在 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.03h， 生成 benzyl N-tert-butyloxycarbonyl-L-γ-glutamate α-N-methylamide
  参考文献：
  名称：

  关于选择阻滞剂的研究。5.基于修饰的丝氨酸-谷氨酸二肽的唾液酸化的Lewis x模拟物的设计，合成和生物学特征。

  摘要：

  我们基于分子模型合理设计了sLe（x）模拟物，合成了II型和II'型β-转二肽（3a，b），并在体外和体内评估了它们的生物学特性。针对E-选择素-sLe（x）结合，II型β-转二肽L-Ser-D-Glu 3a（IC50，13 microM）和II'β-转二肽D-Ser-L-Glu 3b（ IC50（5.5 microM）比sLe（x）（1; IC50，600 microM）和3'-硫酸化Le（x）类似物（2; IC50，280 microM）强效阻滞剂高20-100倍。另一方面，其他立体异构体（例如L-Ser-L-Glu 3c和D-Ser-D-Glu 3d）是非常弱的阻滞剂，3c，d的IC50> 1000 microM。相对于P-和L-选择素，尽管化合物3a-d的立体化学差异很大，但二肽3a-d的阻滞剂均比sLe（x）或化合物2强。在小鼠模型中，化合物3b提供了针对免疫球蛋白E介导的皮肤反

  DOI：

  10.1021/jm970262k

文献信息

• The efficient synthesis of a complex O-phosphoseryl-containing peptide Ac-Glu-PSer-Leu-PSer-P-Ser-PSer-Glu-Glu-NHMe
  作者：John W. Perich、R. B. Johns

  DOI：10.1039/c39880000664

  日期：——

  The title octapeptide was prepared by the synthesis of the fully protected tetra-Ser(PO3Ph2)-octapeptide by incorporation of Boc-Ser(PO3Ph2)-OH (Boc = t-butoxycarbonyl) in conventional Boc/solution phase peptide synthesis, followed by the complete hydrogenolytic cleavage of the phenyl groups from the Ser(PO3Ph2)-octapeptide.

  通过在常规Boc /溶液相中掺入Boc-Ser（PO 3 Ph 2）-OH（Boc =叔丁氧羰基）来合成完全保护的四-Ser （PO 3 Ph 2）-八肽，从而制备标题八肽肽合成，然后完全水解水解Ser（PO 3 Ph 2）-八肽中的苯基。
• Synthesis of Casein-Related Peptides and Phosphopeptides. XVI. The Efficient Synthesis of the Casein-Related O-Phosphoseryl-Containing Peptide Ac-Glu-Ser(P)-Leu-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-NHMe
  作者：JW Perich、RB Johns、EC Reynolds

  DOI：10.1071/ch9920385

  日期：——

  The multiple-O-phosphoseryl-containing peptide, Ac-Glu-Ser (P)-Leu-Ser (P)-Ser (P)-Ser (P)-Glu-Glu-NHMe, was prepared in high yield by the use of Boc-Ser(PO3Ph2)-OH in the Boc mode of peptide synthesis for the preparation of the protected Ser(PO3Ph2)-octapeptide followed by its one-step hydrogenolytic deprotection with platinum oxide. Peptide synthesis was performed by the repetitive excess mixed-anhydride coupling procedure and 40% CF3CO2H/CH2Cl2 for removal of the Boc group from intermediate peptides. The phosphopeptide was found to be greater than 99% pure by C8 r.p.-h.p.1.c. analysis, and was readily characterized by amino acid analysis, 13C n.m.r. spectroscopy and f.a.b. mass spectrometry.

  利用 Boc-Ser(PO3Ph2)-OH 以 Boc 多肽合成模式制备受保护的 Ser(PO3Ph2)-八肽，然后用氧化铂进行一步氢解脱保护，高产制备了含多个 O-膦丝酰基的多肽 Ac-Glu-Ser(P)-Leu-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-NHMe。肽的合成采用重复过量混合酸酐偶联程序和 40% CF3CO2H/CH2Cl2 去除中间肽上的 Boc 基团。通过 C8 r.p.-h.p.1.c.分析发现，磷酸肽的纯度超过 99%，并可通过氨基酸分析、13C n.m.r.光谱和 f.a.b. 质谱分析进行表征。
• FUCOSE DERIVATIVES, DRUGS CONTAINING THE SAME AS ACTIVE INGREDIENT, AND INTERMEDIATES FOR PRODUCING THE SAME
  申请人：KANEBO, LTD.

  公开号：EP0859005A1

  公开（公告）日：1998-08-19

  A compound of the formula (I): wherein X1 is a group of one of the following formulae (1), (2) and (3): R1 is a branched long chain alkyl group, R2 is ―CONHR3, a carboxyl group or a hydrogen atom, n is an integer of 0, 1 or 2, and R3 is a lower alkyl group or a phenyl group, or a pharmaceutically acceptable salt thereof, which is useful as a selectin inhibitor, and can be used in the prophylaxis or treatment of various inflammatory diseases such as inflammatory dermatitis (e.g., atopic dermatitis, contact hypersensitivity, photodermatosis, etc.), autoimmune chronic diseases (e.g. rheumatoid arthritis, chronic thyroiditis, etc.), and ischemia-reperfusion injury.

  式 (I) 的化合物： 其中 X1 是下式（1）、（2）和（3）之一的基团： R1是支链长链烷基，R2是-CONHR3、羧基或氢原子，n是0、1或2的整数，R3是低级烷基或苯基，或其药学上可接受的盐，可作为选择素抑制剂，用于预防或治疗各种炎症性疾病，如炎症性皮炎（如、特应性皮炎、接触性过敏、光敏性皮肤病等）、自身免疫性慢性疾病（如类风湿性关节炎、慢性甲状腺炎等）以及缺血再灌注损伤。
• Synthesis and neuroprotective activity of analogues of glycyl-l-prolyl-l-glutamic acid (GPE) modified at the α-carboxylic acid
  作者：Nicholas S. Trotter、Margaret A. Brimble、Paul W.R. Harris、David J. Callis、Frank Sieg

  DOI：10.1016/j.bmc.2004.10.005

  日期：2005.1

  The synthesis of nine GPE* analogues, wherein the alpha-carboxylic acid group of glutamic acid has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-L-proline 2 with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE. (C) 2004 Elsevier Ltd. All rights reserved.
• Studies on Selectin Blockers. 7. Structure−Activity Relationships of Sialyl Lewis X Mimetics Based on Modified Ser-Glu Dipeptides
  作者：Takahiro Tsukida、Hideki Moriyama、Kiriko Kurokawa、Toshio Achiha、Yoshimasa Inoue、Hirosato Kondo

  DOI：10.1021/jm980267x

  日期：1998.10.1

  We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(x), 1) and a 3'-sulfated Lewis X analogue (2) toward E-selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' beta-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' beta-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(x) mimetics with type II and type II'-beta-turn dipeptides could be a useful methodology for the design of an active selectin blocker.