N-Boc-Tyr(Bzl)-Leu-OMe | 65638-82-6

• 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: N-Boc-Tyr(Bzl)-Leu-OMe
• 英文别名: N-Boc-Tyr(Bn)-Leu-OMe；Boc-Tyr(Bzl)-Leu-OMe；Boc-Tyr(Bn)-Leu-OMe；methyl (2S)-4-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-phenylmethoxyphenyl)propanoyl]amino]pentanoate
• CAS: 65638-82-6
• 化学式: C₂₈H₃₈N₂O₆
• 分子量: 498.62
• InChiKey: ZVDRRSNUEZFDFT-ZEQRLZLVSA-N

物化性质

• 熔点：
  109-111 °C(Solv: isopropanol (67-63-0))
• 沸点：
  658.4±55.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  36
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-Boc-Tyr(Bzl)-Leu-OMe 在 lithium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 N-Boc-Tyr(Bn)-Leu-Trp-NHPh
  参考文献：
  名称：

  Linear TMC-95-Based Proteasome Inhibitors

  摘要：

  We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and termini greatly influenced both the efficiency and selectivity of action on a given type of active site. Inhibition constants were submicromolar (K-i approximate to 300 nM) despite the absence of the entropically favorable constrained conformation that is characteristic of TMC-95A and its cyclic analogues. These linear compounds were readily prepared and reasonably stable in culture medium and could be optimized to inhibit one, two, or all three proteasome catalytic sites. Cytotoxicity assays performed on a series of human tumor cell lines identified the most potent inhibitors in cells.

  DOI：

  10.1021/jm0701324
• 作为产物：
  描述：

  Boc-O-苄基-L-酪氨酸 、 L-亮氨酸甲酯盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 N-Boc-Tyr(Bzl)-Leu-OMe
  参考文献：
  名称：

  NOVEL SMALL MOLECULE DNAK INHIBITORS

  摘要：

  抑制HSP70蛋白的方法，导致抑制HSP70蛋白的药剂，以及这种抑制对细胞增殖的影响。本文还披露了包含小分子或其药用盐的抗微生物药剂，以及其进一步的使用方法。所披露的小分子或其药用盐对微生物中的分子伴侣活性具有抑制作用，例如HSP70同源物。所披露的小分子或其药用盐还对癌症的治疗治疗有效。

  公开号：

  US20100087466A1

文献信息

• Environmentally benign peptide synthesis using liquid-assisted ball-milling: application to the synthesis of Leu-enkephalin
  作者：Julien Bonnamour、Thomas-Xavier Métro、Jean Martinez、Frédéric Lamaty

  DOI：10.1039/c3gc40302e

  日期：——

  This paper describes an original methodology for peptide bond synthesis avoiding toxic solvents and reactants. Ball-milling stoichiometric amounts of Boc-protected α-amino acid N-carboxyanhydrides (Boc-AA-NCA) or Boc-protected α-amino acid N-hydroxysuccinimide esters (Boc-AA-OSu) with α-amino acid alkyl ester salts in the presence of NaHCO3 and a minimal quantity of EtOAc led to the production of di-

  本文介绍了一种原始的方法 肽 避免毒性的键合成 溶剂和反应物。球-铣削在存在下，Boc保护的α-氨基酸N-羧基酸酐（Boc-AA-NCA）或Boc保护的α-氨基酸N-羟基琥珀酰亚胺酯（Boc-AA-OSu）的化学计量的NaHCO 3和最少量的EtOAc导致生成二甲苯五肽以有效和环保的方式。该方法已成功应用于亮脑啡肽的合成。
• Synthesis of Macrocyclic Peptide Analogues of Proteasome Inhibitor TMC-95A
  作者：Alexandra Berthelot、Sandrine Piguel、Gwennaël Le Dour、Joëlle Vidal

  DOI：10.1021/jo035256c

  日期：2003.12.1

  The synthesis of three constrained macrocyclic peptide analogues 1 of TMC-95A as potential proteasome inhibitors is described. The key step involves a Ni(0)-mediated macrocyclization of tripeptides 2 bearing halogenated aromatic side chains for the formation of the biaryl junction. In addition, an enantioselective preparation of l-7-bromotryptophan methyl ester 3 using a Corey-O'Donnell alkylation

  描述了作为潜在的蛋白酶体抑制剂的TMC-95A的三种受限大环肽类似物1的合成。关键步骤涉及Ni（0）介导的三肽2的大环化，该三肽2带有卤化芳族侧链，用于形成联芳基。另外，以良好的总收率和以非常高的ee（＞ 85％）在多克规模上获得了使用甘氨酸二苯甲酮亚胺的Corey-O'Donnell烷基化的1-7-溴色氨酸甲酯3的对映选择性制备。
• Compounds Useful as Modulators of the Proteasome Activity
  申请人：Reboud-Ravaux Michele Claude Yvonne

  公开号：US20090069222A1

  公开（公告）日：2009-03-12

  The present invention relates to the use of compounds of the following general formula (I): wherein n o is 0 or 1, and when n o is 1, X=CH 2 or X=NCH 2 C 6 H 5 ; R 1 is OH, or a OR 10 group, or a group of formula NH—(CH 2 ) n1 —R 11 ; R 2 is H, or an alkyl group, or a group of formula (CH 2 ) n2 —(CO) n3 —NR 13 R 14 ; R 3 is H, or an alkyl group; R 4 is H, or Boc, or Z; R 5 is H, or Boc, or Z; R 6 is a OR 16 group; R 7 and R 8 are H, or a halogen atom, as modulators of the proteasome activity, in the frame of the preparation of a medicament useful for the prevention or treatment of diseases wherein the proteasome is involved, or the preparation of cosmetic compositions, or of phytosanitary compositions

  本发明涉及使用以下通式（I）的化合物：其中nois为0或1，当nois为1时，X=CH2或X=NCH2C6H5; R1为OH，或OR10基团，或公式NH—（CH2）n1—R11的基团; R2为H，或烷基，或公式（CH2）n2—（CO）n3—NR13R14的基团; R3为H，或烷基; R4为H，或Boc，或Z; R5为H，或Boc，或Z; R6为OR16基团; R7和R8为H，或卤原子，作为蛋白酶体活性调节剂，用于制备用于预防或治疗蛋白酶体参与的疾病的药物，或制备化妆品组合物或植物保护组合物。
• Compounds useful as modulators of the proteasome activity
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：US07919468B2

  公开（公告）日：2011-04-05

  Compounds of the following general formula (I): are provided. The compounds can be used as modulators of the proteasome activity, in the preparation of a medicament useful for the prevention or treatment of diseases wherein the proteasome is involved, such as diseases of inflammatory processes, various hematological and solid tumor cancers, immunological and autoimmune diseases, cardiac pathologies, myopathies, AIDS, cystic fibrosis, Alzheimer's and Parkinson's disease, or in the preparation of cosmetic compositions or phytosanitary compositions.

  提供了以下一般式（I）的化合物。这些化合物可用作蛋白酶体活性的调节剂，用于制备有用于预防或治疗蛋白酶体参与的疾病的药物，如炎症过程疾病、各种血液和实体肿瘤癌症、免疫和自身免疫性疾病、心脏病理学、肌病、艾滋病、囊性纤维化、阿尔茨海默病和帕金森病，或用于制备化妆品组合物或植物保护组合物。
• Synthese des Insulin-Sequenzabsehnittes B15-27 (Ala 27) in geschützter Form
  作者：Bernd Schwenzer、Günter Kempe、Günter Losse

  DOI：10.1002/zfch.19810210611

  日期：1981.6