Fmoc-Pro anhydride | 76571-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Pro anhydride
• 英文别名: 2-O-[(2S)-1-(9H-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carbonyl] 1-O-(9H-fluoren-9-ylmethyl) (2S)-pyrrolidine-1,2-dicarboxylate
• CAS: 76571-69-2
• 化学式: C₄₀H₃₆N₂O₇
• 分子量: 656.735
• InChiKey: AGWQGSMHSPXBSA-ZPGRZCPFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  49
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Fmoc-Pro anhydride 在 哌啶 、 N-甲基吡咯烷酮 作用下， 反应 4.83h， 生成 <4S-(4α,12aα)>-9-(L-prolylamino)-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide
  参考文献：
  名称：

  "Glycylcyclines". 3. 9-Aminodoxycyclinecarboxamides

  摘要：

  A series of 9-(acylamino)doxycycline derivatives has been prepared. These analogs exhibit good activity against both tetracycline sensitive and tetracycline resistant Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria that are encoded with the efflux and ribosomal resistance gene factors. N,N-Dialkylglycylamido derivatives possessed the highest activity. Replacement of glycine moiety with other amino acids did not further enhance the activity.

  DOI：

  10.1021/jm00046a003
• 作为产物：
  描述：

  Fmoc-L-脯氨酸 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 Fmoc-Pro anhydride
  参考文献：
  名称：

  Atherton, Eric; Sheppard, Robert C.; Ward, Peter, Journal of the Chemical Society. Perkin transactions I, 1985, p. 2065 - 2074

  摘要：

  DOI：

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
• Solid-Phase Synthesis of Arylpiperazine Derivatives and Implementation of the Distributed Drug Discovery (D3) Project in the Search for CNS Agents
  作者：Paweł Zajdel、Joanna Król、Katarzyna Grychowska、Maciej Pawłowski、Gilles Subra、Gaël Nomezine、Jean Martinez、Grzegorz Satała、Andrzej J. Bojarski、Ziniu Zhou、Martin J. O’Donnell、William L. Scott

  DOI：10.3390/molecules16054104

  日期：——

  We have successfully implemented the concept of Distributed Drug Discovery (D3) in the search for CNS agents. Herein, we demonstrate, for the first time, student engagement from different sites around the globe in the development of new biologically active compounds. As an outcome we have synthesized a 24-membered library of arylpiperazine derivatives targeted to 5-HT1A and 5-HT2A receptors. The synthesis was simultaneously performed on BAL-MBHA-PS resin in Poland and the United States, and on BAL-PS-SynPhase Lanterns in France. The D3 project strategy opens the possibility of obtaining potent 5-HT1A/5-HT2A agents in a distributed fashion. While the biological testing is still centralized, this combination of distributed synthesis with screening will enable a D3 network of students world-wide to participate, as part of their education, in the synthesis and testing of this class of biologically active compounds.

  我们已成功实施了分布式药物发现（D3）概念，以寻找中枢神经系统药物。本文首次展示了来自全球不同地点的学生参与到新型生物活性化合物的研发中。作为成果，我们合成了一系列以5-HT1A和5-HT2A受体为靶点的24个芳基哌嗪衍生物库。合成过程在波兰和美国同时使用BAL-MBHA-PS树脂进行，在法国则采用BAL-PS-SynPhase灯笼树脂。D3项目策略为以分布式方式获得强效5-HT1A/5-HT2A配体提供了可能。尽管生物测试仍集中进行，但这种结合分布式合成与筛选的模式将使全球学生的D3网络能够参与其中，作为其教育的一部分，共同进行该类生物活性化合物的合成与测试。
• Convergent solid phase peptide synthesis. I. Synthesis of protected segments on a hydroxymethylphenyloxymethyl resin using the base labile FMOC α-amine protection. Model synthesis of LHRH.
  作者：E. Pedroso、A. Grandas、M.A. Saralegui、E. Giralt、C. Granier、J. van Rietschoten

  DOI：10.1016/0040-4020(82)85102-8

  日期：1982.1

  solid phase peptide synthesis has been applied to yield LHRH. The segments 1–6 and 7–10 of LHRH were synthesized on a hydroxymethylphenyloxymethyl resin using the base labile Fmoc protecting group on the α-amines. The side chains were protected by HF labile groups. Purification of the segments was performed on Sephadex LH-20 columns and by HPLC on Silica Gel 60 columns. The two segments were then assembled

  收敛固相肽合成已用于产生LHRH。LHRH的1–6和7–10片段是使用α-胺上的碱不稳定Fmoc保护基在羟甲基苯氧基甲基树脂上合成的。侧链受到H​​F不稳定基团的保护。片段的纯化在Sephadex LH-20柱上进行，并且通过HPLC在硅胶60柱上进行。然后将两个片段组装在α-氨基苄基树脂上以产生LHRH的完整序列。经Sephadex G-15和羧甲基纤维素CM-52进行HF处理并标准纯化后，获得所需的LHRH。通过相同的策略在咔唑基氧基甲基苯基氧基甲基树脂上合成链段显示出意想不到的困难。
• Atherton, Eric; Pinori, Masimo; Sheppard, Robert C., Journal of the Chemical Society. Perkin transactions I, 1985, p. 2057 - 2064
  作者：Atherton, Eric、Pinori, Masimo、Sheppard, Robert C.

  DOI：——

  日期：——
• Cyclic peptides as selective tachykinin antagonists
  作者：Brian J. Williams、Neil R. Curtis、Alexander T. McKnight、Janet J. Maguire、Stephen C. Young、Daniel F. Veber、Raymond Baker

  DOI：10.1021/jm00053a001

  日期：1993.1

  Twenty homodetic cyclic peptides based on the C-terminal sequence of substance P were prepared (Table I) by a combination of solid-phase techniques and cyclizations using azide coupling Incorporation of dipeptide mimics based on substituted gamma-lactams were used in some cases to restrict their conformational mobility. Five of these cyclic peptides were shown to have high tachykinin antagonist activity (pA2 > 6) at NK-2 receptors (rat vas deferens). The two most potent of this series, XVII, cyclo(Gln-Trp-Phe-Gly-Leu-Met) (pA2 = 8.1), and I cyclo(Gln-Trp-Phe-(R)Gly[ANC-2]Leu-Met) (pA2 = 6.7), were selective for NK-2 receptors compared with the other tachykinin receptors (Table II).