2,5-二氧代-1-吡咯烷基 N-[(9H-芴-9-基甲氧基)羰基]-O-(2-甲基-2-丙基)酪氨酸酯 | 155892-27-6

• 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
• 中文名称: 2,5-二氧代-1-吡咯烷基 N-[(9H-芴-9-基甲氧基)羰基]-O-(2-甲基-2-丙基)酪氨酸酯
• 中文别名: 2,5-二氧代-1-吡咯烷基N-[(9H-芴-9-基甲氧基)羰基]-O-(2-甲基-2-丙基)酪氨酸酯
• 英文名称: Fmoc-Tyr(tBu)-OSu
• 英文别名: Fmoc-L-Tyr(tBu)-OSu；(2,5-dioxopyrrolidin-1-yl) (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoate
• CAS: 155892-27-6
• 化学式: C₃₂H₃₂N₂O₇
• 分子量: 556.615
• InChiKey: FFYIKTNTHOGOIE-MHZLTWQESA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,5-二氧代-1-吡咯烷基 N-[(9H-芴-9-基甲氧基)羰基]-O-(2-甲基-2-丙基)酪氨酸酯 在 sodium hydrogen sulfide 、 15-冠醚-5 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 Fmoc-Tyr(Bu^t)-SH
  参考文献：
  名称：

  通过固相肽合成将多个硫酰胺取代基位点特异性结合到肽主链中。

  摘要：

  在各种肽修饰策略中，通过用硫原子取代酰胺键的羰基氧原子进行硫酰胺取代，对于化学生物学而言是不可估量的工具，可用于肽药物发现和蛋白质结构功能研究。然而，由于缺乏用于位点特异性地将硫酰胺键结合到肽主链中，特别是将多个硫酰胺取代引入到固体支持物上的肽的合成方法，所以尚未对硫酰胺取代作用进行很好的研究。在此，我们报告了一种高效的方法，该方法通过使用α-硫代酰氧基烯酰胺（通过添加N保护的单硫代氨基酸和乙酰胺形成）以位点特异性的方式将硫酰胺键结合到肽主链中，作为固相肽合成中的新型硫酰化试剂。此方法适用于20个蛋白原氨基酸中的19个，His是一个例外。可以将一个至多个硫酰胺取代基掺入正在生长的肽中，而没有差向异构化或低水平的差向异构化。通过使用该方法，可以平滑地合成包含多达五个连续硫代酰胺键的完全硫代酰胺取代的六肽。这种合成方法将刺激硫酰胺取代工具在蛋白质工程和肽药物发现中的应用。可以顺利合成含多达五个

  DOI：

  10.1021/acs.joc.9b02486
• 作为产物：
  描述：

  Nε-Boc-Nα-Cbz-L-赖氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 在 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 2,5-二氧代-1-吡咯烷基 N-[(9H-芴-9-基甲氧基)羰基]-O-(2-甲基-2-丙基)酪氨酸酯
  参考文献：
  名称：

  Somatostatin Receptor-Binding Peptides Labeled with Technetium-99m:  Chemistry and Initial Biological Studies

  摘要：

  The synthesis of peptides which possess a high affinity for the somatostatin receptor and contain a chelator for the radionuclide technetium-99m is described. The target compounds were designed such that they would form stable, oxotechnetium(V) chelate complexes in which the site of metal coordination was well defined and remote from the receptor-binding region. Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Peptide oxorhenium complexes and Tc-99m complexes eluted closely upon HPLC analysis. The receptor-binding affinities of both the free and rhenium-coordinated species were measured in vitro. The binding affinities of the free peptides (K-i's in the 0.25-10 nM range) compared favorably with [DTPA]octreotide (K-i = 1.6 nM), which, as the indium-lll complex, is already approved for somatostatin receptor (SSTR)-expressing tumor imaging in the United States and Europe. Furthermore, the rhenium-coordinated peptides had binding affinities which, in many cases, were higher than those of the corresponding free peptides, with several complexes having a K-i's of 0.1 nM. Some of the more potent SSTR-binding peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The Tc-99m-labeled peptides prepared in this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, because they are low molecular weight peptides, expected pharmacokinetics characterized by rapid tracer excretion from the body resulting in high-contrast images.

  DOI：

  10.1021/jm950111m

文献信息

• Kilogram-Scale Synthesis of Osteogenic Growth Peptide (10–14) Using a Fragment Coupling Approach
  作者：Teng Zhang、Zhenxing Chen、Yan Tian、Bin Han、Ning Zhang、Wei Song、Zhulan Liu、Jinli Zhao、Jianli Liu

  DOI：10.1021/acs.oprd.5b00004

  日期：2015.9.18

  Kilogram-scale synthesis of a bioactive pentapeptide in solution by “3 + 2” fragment coupling strategy has been successively accomplished in the development of OGP (10–14), a minimal OGP-derived sequence that retains the full proliferative activity of the osteogenic growth peptide. The synthetic scheme, coupling conditions, and scaling-up of the process are systematically studied; the epimerization

  通过“ 3 + 2”片段偶联策略在溶液中公斤级合成生物活性五肽已在OGP（10–14）的开发中成功完成，OGP是最小的OGP衍生序列，保留了成骨生长的全部增殖活性肽。系统地研究了合成方案，偶联条件和工艺放大。还评估了三肽片段和五肽的差向异构化。
• Somatostatin Receptor-Binding Peptides Labeled with Technetium-99m:  Chemistry and Initial Biological Studies
  作者：Daniel A. Pearson、John Lister-James、William J. McBride、David M. Wilson、Lawrence J. Martel、Edgar R. Civitello、John E. Taylor、Brian R. Moyer、Richard T. Dean

  DOI：10.1021/jm950111m

  日期：1996.1.1

  The synthesis of peptides which possess a high affinity for the somatostatin receptor and contain a chelator for the radionuclide technetium-99m is described. The target compounds were designed such that they would form stable, oxotechnetium(V) chelate complexes in which the site of metal coordination was well defined and remote from the receptor-binding region. Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Peptide oxorhenium complexes and Tc-99m complexes eluted closely upon HPLC analysis. The receptor-binding affinities of both the free and rhenium-coordinated species were measured in vitro. The binding affinities of the free peptides (K-i's in the 0.25-10 nM range) compared favorably with [DTPA]octreotide (K-i = 1.6 nM), which, as the indium-lll complex, is already approved for somatostatin receptor (SSTR)-expressing tumor imaging in the United States and Europe. Furthermore, the rhenium-coordinated peptides had binding affinities which, in many cases, were higher than those of the corresponding free peptides, with several complexes having a K-i's of 0.1 nM. Some of the more potent SSTR-binding peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The Tc-99m-labeled peptides prepared in this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, because they are low molecular weight peptides, expected pharmacokinetics characterized by rapid tracer excretion from the body resulting in high-contrast images.
• Site-Specific Incorporation of Multiple Thioamide Substitutions into a Peptide Backbone via Solid Phase Peptide Synthesis
  作者：Jinhua Yang、Changliu Wang、Chaochao Yao、Chunqiu Chen、Yafang Hu、Guifeng He、Junfeng Zhao

  DOI：10.1021/acs.joc.9b02486

  日期：2020.2.7

  as novel thioacylating reagents in solid phase peptide synthesis. This method is amenable for 19 of 20 proteinogenic amino acids, His being the exception. One to multiple thioamide substitutions could be incorporated into a growing peptide with no epimerization or a low level of epimerization. By using this method, a fully thioamide-substituted hexapeptide containing up to five continuous thioamide

  在各种肽修饰策略中，通过用硫原子取代酰胺键的羰基氧原子进行硫酰胺取代，对于化学生物学而言是不可估量的工具，可用于肽药物发现和蛋白质结构功能研究。然而，由于缺乏用于位点特异性地将硫酰胺键结合到肽主链中，特别是将多个硫酰胺取代引入到固体支持物上的肽的合成方法，所以尚未对硫酰胺取代作用进行很好的研究。在此，我们报告了一种高效的方法，该方法通过使用α-硫代酰氧基烯酰胺（通过添加N保护的单硫代氨基酸和乙酰胺形成）以位点特异性的方式将硫酰胺键结合到肽主链中，作为固相肽合成中的新型硫酰化试剂。此方法适用于20个蛋白原氨基酸中的19个，His是一个例外。可以将一个至多个硫酰胺取代基掺入正在生长的肽中，而没有差向异构化或低水平的差向异构化。通过使用该方法，可以平滑地合成包含多达五个连续硫代酰胺键的完全硫代酰胺取代的六肽。这种合成方法将刺激硫酰胺取代工具在蛋白质工程和肽药物发现中的应用。可以顺利合成含多达五个