N5-[[[(3,4-二氢-2,2,5,7,8-五甲基-2H-1-苯并吡喃-6-基)磺酰基]氨基]亚氨基甲基]-N2-[(9H-芴-9-基甲氧基)羰基]-L-鸟氨酸五氟苯基酯 | 136013-81-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N5-[[[(3,4-二氢-2,2,5,7,8-五甲基-2H-1-苯并吡喃-6-基)磺酰基]氨基]亚氨基甲基]-N2-[(9H-芴-9-基甲氧基)羰基]-L-鸟氨酸五氟苯基酯
• 英文名称: Fmoc-Arg(PMC)-OC6F5
• 英文别名: Fmoc-Arg(Pmc)-OPfp；Perfluorophenyl N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-Nw-((2,2,5,7,8-pentamethylchroman-6-yl)sulfonyl)-L-argininate；(2,3,4,5,6-pentafluorophenyl) (2S)-5-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoate
• CAS: 136013-81-5
• 化学式: C₄₁H₄₁F₅N₄O₇S
• 分子量: 828.857
• InChiKey: WMUBZSPLEATQKR-LJAQVGFWSA-N

物化性质

• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  58
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  167
• 氢给体数：
  3
• 氢受体数：
  13

制备方法与用途

制备方法

1. 用作医药中间体

用途简介

暂无具体信息。

用途

1. 用作医药中间体

反应信息

• 作为反应物：
  描述：

  N5-[[[(3,4-二氢-2,2,5,7,8-五甲基-2H-1-苯并吡喃-6-基)磺酰基]氨基]亚氨基甲基]-N2-[(9H-芴-9-基甲氧基)羰基]-L-鸟氨酸五氟苯基酯 、 3-[7-(2-tert-butoxycarbonylamino-ethyl)-1,3,6,8-tetraoxo-3,6,7,8-tetrahydro-1H-benzo[lmn][3,8]phenanthrolin-2-yl]-propionic acid 在 三氟乙酸 、 2,6-二甲基吡啶 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 N-2-(N-α-9-fluorenylmethoxycarbonyl-N^G-2,2,5,7,8-pentamethylchroman-6-sulfonyl-L-argyl)aminoethyl-N'-(2-carboxyethyl)-1,4,5,8-naphthalenetetracarboxylic diimide
  参考文献：
  名称：

  The synthesis and screening of 1,4,5,8-naphthalenetetracarboxylic diimide–peptide conjugates with antibacterial activity

  摘要：

  We have employed an initial combinatorial approach followed by systematic lead optimization to investigate a series of novel molecules that exhibit antimicrobial activity against Gram-negative and Gram-positive bacteria. The new molecules contain various sequences of amino acids, generally L-lysine and glycine, attached to the 1,4,5,8-naphthalenetetracarboxylic diimide aromatic unit. Systematic structure-activity studies found that increasing positive charge enhanced activity and molecules containing one naphthalenetetracarboxylic diimide unit as well as at least seven lysine residues were optimum for antimicrobial activity. The naphthalenetetracarboxylic diimide derivatives were found to be inactive against mammalian cell lines, making them excellent antimicrobial candidates. Our results indicate that combining positive charge with aromatic and/or hydrophobic elements may be an interesting new approach to antimicrobial agents and adds an important new dimension to the field of cationic peptides. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00108-0

文献信息

• Structure-Activity Relationships of Cyclic Pentapeptide Endothelin A Receptor Antagonists
  作者：Takehiro Fukami、Toshio Nagase、Kagari Fujita、Takashi Hayama、Kenji Niiyama、Toshiaki Mase、Shigeru Nakajima、Takahiro Fukuroda、Toshihiko Saeki

  DOI：10.1021/jm00021a021

  日期：1995.10

  D-heteroarylglycine was preferable at this position. Among synthesized cyclic pentapeptides, compound 36 (BQ-518) was the most potent ETA receptor antagonist, with a pA2 of 8.1 against ET-1-induced vasoconstriction in isolated porcine coronary arteries. This compound also showed the greatest selectivity between ETA and ETB receptors (IC50 for human ETA = 1.2 nM, IC50 for human ETB = 55 microM). In contrast, compound

  天然产物内皮素A（ETA）受体拮抗剂的类似物环（-D-Trp1-D-Glu2-Ala3-D-Val4-Leu5-）（1）和环（-D-Trp1-D-Glu2-Ala3-D -alloIle4-Leu5-）（2）的制备和测试对[125I]内皮素（ET-1）与蛋白质ETA受体结合的抑制活性。天然产物的DDLDL手性序列似乎对于抑制活性至关重要，因为D-Trp或D-Glu（或两者）在1中转化为相应的L-异构体消除了该特性。在天然产物的每个位置上的系统修饰阐明了结构-活性关系，并导致了高效和选择性的ETA受体拮抗剂。D-Trp1和Leu5多数被其他氨基酸替代导致抑制活性的显着降低。相反，用D-Asp2替代D-Glu2增强了活性。关于Ala3的位置，所有具有亚氨基酸的类似物，无论是环状的还是无环的，都比氨基酸类似物具有更高的亲和力。另外，大多数在其侧链中具有各种官能团的氨基酸替代物并未显着改变ETA结合亲和力。D-Val4
• α-Ketocarbonyl Peptides:  A General Approach to Reactive Resin-Bound Intermediates in the Synthesis of Peptide Isosteres for Protease Inhibitor Screening on Solid Support
  作者：Alexandra Papanikos、Jörg Rademann、Morten Meldal

  DOI：10.1021/ja003690f

  日期：2001.3.1

  highly reactive terminal ketocarbonyls were prone to aldol-type dimerization and could be transferred into stable moieties by oxime formation, reduction to the alcohol, or reductive amination, respectively. The alpha-ketocarbonyl peptides were efficient in nucleophilic addition of C-nucleophiles such as phosphono-ylides and allylsilanes.

  α-酮羰基肽是通过金属离子催化的转氨作用从固体支持物上的肽前体生成的。反应在 2 小时内完成，乙醛酸盐作为亲电子试剂，铜 (II) 离子作为催化剂，在 pH 5.5-6.0 的醋酸水溶液缓冲液中。各种天然存在的 α-氨基酸底物产生了一组不同的差异功能化酮。高度反应性的末端酮羰基易于发生羟醛型二聚反应，并且可以分别通过肟形成、还原为醇或还原胺化而转化为稳定的部分。α-酮羰基肽在 C-亲核试剂的亲核加成中是有效的，例如膦酰基内酯和烯丙基硅烷。
• Peptido-organic Diels–Alder reactions on hydrophilic resin: scope for combinatorial chemistry
  作者：Anette Graven、Morten Meldal

  DOI：10.1039/b103765j

  日期：2001.11.29

  A simple route to activated dienes generated from enone precursors at the N-terminal of immobilised dipeptides is described. The dienes are subjected to reaction with a maleimide dieneophile containing a protected amino functionality for continued peptide synthesis. The reactions are pure and quantitative with dienes generated at the N-terminal of a variety of different dipeptides, including substrates

  从中生成活化二烯的简单途径 烯酮 固定化N末端的前体 二肽描述。使二烯与马来酰亚胺 含有受保护的亲二烯体 氨基 继续功能 肽合成。反应是纯的和定量的，二烯在各种不同的N端生成二肽，包括含有 氨基酸具有受保护的侧链功能。在提出的工作中，亲水性POEPOP树脂被用作固体载体。本文还描述了通过Mitsunobu反应将树脂羟基官能团官能团交换为叠氮基的高产方法，然后进行减少 产生氨基官能化的POEPOP。
• The synthesis and screening of 1,4,5,8-naphthalenetetracarboxylic diimide–peptide conjugates with antibacterial activity
  作者：Chandra T Miller、Ramal Weragoda、Elzbieta Izbicka、Brent L Iverson

  DOI：10.1016/s0968-0896(01)00108-0

  日期：2001.8

  We have employed an initial combinatorial approach followed by systematic lead optimization to investigate a series of novel molecules that exhibit antimicrobial activity against Gram-negative and Gram-positive bacteria. The new molecules contain various sequences of amino acids, generally L-lysine and glycine, attached to the 1,4,5,8-naphthalenetetracarboxylic diimide aromatic unit. Systematic structure-activity studies found that increasing positive charge enhanced activity and molecules containing one naphthalenetetracarboxylic diimide unit as well as at least seven lysine residues were optimum for antimicrobial activity. The naphthalenetetracarboxylic diimide derivatives were found to be inactive against mammalian cell lines, making them excellent antimicrobial candidates. Our results indicate that combining positive charge with aromatic and/or hydrophobic elements may be an interesting new approach to antimicrobial agents and adds an important new dimension to the field of cationic peptides. (C) 2001 Elsevier Science Ltd. All rights reserved.