Fmoc-Iva-OH | 160885-93-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Iva-OH
• 英文别名: N-Fmoc-DL-isovaline；2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-methylbutanoic acid
• CAS: 160885-93-8
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: DZSLHAJXIQCMLR-UHFFFAOYSA-N

物化性质

• 熔点：
  105-107 °C
• 沸点：
  551.8±33.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Fmoc-Iva-OH 在 吡啶 、 三聚氟氰 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以87%的产率得到Fmoc-Iva-F
  参考文献：
  名称：

  An Automatic Solid-Phase Synthesis of Peptaibols

  摘要：

  An automated approach to peptaibols using microwave-assisted solid-phase peptide synthesis is demonstrated with a combination of HBTU and acid fluoride mediated couplings for normal and alpha,alpha-dialkylated amino acids, respectively. The method is utilized for the automated synthesis of several full-length peptaibols, including alamethicin, tylopeptin, ampullosporin, bergofungin, cervinin, trikoningin, trichogin, and peptaibolin, reducing both synthesis time and costs significantly as compared to other approaches. Furthermore, the use of noncommercially available reagents is minimized.

  DOI：

  10.1021/jo802058x
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 2-氨基-2-甲基丁酸盐酸盐 在 水 、 sodium carbonate 、 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以84%的产率得到Fmoc-Iva-OH
  参考文献：
  名称：

  An Automatic Solid-Phase Synthesis of Peptaibols

  摘要：

  An automated approach to peptaibols using microwave-assisted solid-phase peptide synthesis is demonstrated with a combination of HBTU and acid fluoride mediated couplings for normal and alpha,alpha-dialkylated amino acids, respectively. The method is utilized for the automated synthesis of several full-length peptaibols, including alamethicin, tylopeptin, ampullosporin, bergofungin, cervinin, trikoningin, trichogin, and peptaibolin, reducing both synthesis time and costs significantly as compared to other approaches. Furthermore, the use of noncommercially available reagents is minimized.

  DOI：

  10.1021/jo802058x

文献信息

• Design and Discovery of Novel Cyclic Peptides as EDPs–EBP Interaction Inhibitors for the Treatment of Liver Fibrosis
  作者：Nazi Song、Haonan Li、Qinglin Tang、Suijia Luo、Zihan Shi、Qian Zhao、Runkai Li、Yili Chen、Xiaoqing Cai、Xianxing Jiang

  DOI：10.1021/acs.jmedchem.2c01764

  日期：——

  efficacy in ameliorating CCl4-induced liver fibrosis. This work provides a successful pharmacological strategy for the development of novel inhibitors of EDPs–EBP interaction, which sheds new light on how cyclic peptides disrupt peptide–protein interaction and may also provide new structure-oriented therapeutic candidates in liver fibrosis.

  肝纤维化是细胞外基质 (ECM) 过度沉积的不良结果，而弹性蛋白被认为是 ECM 的关键成分之一。在特定的病理条件下，弹性蛋白发生降解产生弹性蛋白衍生肽（elastin-derived peptides，EDPs），与弹性蛋白结合蛋白（elastin-binding protein，EBP）结合激活相应的信号通路，从而加速纤维化进程。在此，我们描述了新型环肽的发现，这些环肽可作为有效且稳定的抑制剂来干扰 EDP 和 EBP 之间的肽-蛋白质相互作用。值得注意的是，C XJ -2表现出抑制 PI3K/ERK 通路和减少肝星状细胞增殖和迁移的有效活性。随后的体内研究表明，C XJ-2在改善 CCl 4诱导的肝纤维化方面具有有效的抗纤维化功效。这项工作为开发 EDPs-EBP 相互作用的新型抑制剂提供了成功的药理学策略，这为环肽如何破坏肽-蛋白质相互作用提供了新的思路，也可能为肝纤维化提供新的结构导向治疗候选药物。
• Stepwise Automated Solid Phase Synthesis of Naturally Occurring Peptaibols Using FMOC Amino Acid Fluorides
  作者：Holger Wenschuh、Michael Beyermann、Hanka Haber、Joachim K. Seydel、Eberhard Krause、Michael Bienert、Louis A. Carpino、Ayman El-Faham、Fernando Albericio

  DOI：10.1021/jo00107a020

  日期：1995.1

  The standard methods of stepwise solid phase synthesis according to Merrifield could not previously be applied to the synthesis of the important naturally occurring peptaibols because of difficulties arising from the pronounced steric hindrance caused by alpha,alpha-dialkylated amino acids (incomplete coupling, especially to adjacent similarly constituted units, racemization due to slow coupling to hindered amino acids, etc.), chain degradation due to the presence of acid-labile Aib-Pro linkages, and the lack of any general method for the loading of C-terminal amino alcohols to resin supports. Following recent work on model systems, it is now shown that the adoption of Fmoc amino acid fluorides as coupling reagents makes possible the facile, general assembly of such peptides. The method was demonstrated for alamethicin F30 and F50, saturnisporin SA III, and trichotoxin A50-J. The crude products were of remarkable purity. Amino acid analysis, mass spectral data, and comparison of the synthetic alamethicins with samples of naturally occurring material confirmed the success of the syntheses. No significant amount of racemization (<0.8%) was found for any of the chiral amino acids present. The first step of the synthesis involved a new general method for assembly of C-terminal peptide alcohols via the use of 0-chlorotrityl resin. In addition, model studies on the question of racemization during the coupling of Fmoc amino acid fluorides are reported.
• Synthesis and biological activity of nociceptin/orphanin FQ analogues substituted in position 7 or 11 with Cα,α-dialkylated amino acids
  作者：Marika Arduin、Barbara Spagnolo、Girolamo Calò、Remo Guerrini、Giacomo Carrà、Carmela Fischetti、Claudio Trapella、Erika Marzola、John McDonald、David G. Lambert、Domenico Regoli、Severo Salvadori

  DOI：10.1016/j.bmc.2007.04.026

  日期：2007.7

  Previous structure-activity and NMR studies on nociceptin/orphanin FQ (N/OFQ) demonstrated that Aib substitution of Ala(7) and/or Ala(11) increases the peptide potency through an alpha helix structure induction mechanism. On these bases we synthesised and evaluated pharmacologically in the mouse vas deferens assay a series of N/OFQ-NH2 analogues substituted in position 7 and 11 with C alpha,alpha-disubstituted cyclic, linear and branched amino acids. None of the 20 novel N/OFQ analogues produced better results than [Aib(7)]N/OFQ-NH2. Thus, this substitution was combined with other chemical modifications known to modulate peptide potency and/or efficacy generating compound 21 [Nphe(1)Aib(7) Arg(14) Lys(15)] N/OFQ-NH2 (coded as UFP- 111), compound 22 [(pF)Phe(4) Aib(7) Arg(14) Lys(15)] N/OFQ-NH2 (UFP-112) and compound 23 [Phe psi(CH2-NH)Gly(2) (pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH2 (UFP- 113). These novel peptides behaved as highly potent NOP receptor ligands showing full (UFP- 112) and partial (UFP- 113) agonist and pure antagonist (UFP- 111) activities in a series of in vitro functional assays performed on pharmacological preparations expressing native as well as recombinant NOP receptors. (c) 2007 Elsevier Ltd. All rights reserved.