L-N^α-benzyloxycarbonyl-4-[1-(2-ethenyl)]phenylalanine benzyl ester | 257628-01-6

• 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: L-N^α-benzyloxycarbonyl-4-[1-(2-ethenyl)]phenylalanine benzyl ester
• 英文别名: Cbz-Tyr(Tf)-Bzl；benzyl (2S)-3-(4-ethenylphenyl)-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 257628-01-6
• 化学式: C₂₆H₂₅NO₄
• 分子量: 415.489
• InChiKey: UBVYGSZFDZSUTG-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-N^α-benzyloxycarbonyl-4-[1-(2-ethenyl)]phenylalanine benzyl ester 在 钯 六甲基磷酰三胺 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 乙醇 、 四溴化碳 、 氢气 、 N-甲基吗啉氧化物 、 三苯基膦 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙腈 、 叔丁醇 为溶剂， 反应 8.33h， 生成 L-4-((di-tert-butyl)phosphonomethyl)phenylalanine
  参考文献：
  名称：

  Preparation of l-Nα-Fmoc-4-[di-(tert-butyl)phosphonomethyl]phenylalanine from l-tyrosine

  摘要：

  The unnatural amino acid analogue, 4-(phosphonomethyl)phenylalanine (Pmp, 2), has proven to be a valuable tool for studying protein-tyrosine kinase dependent signal transduction, where it is most often incorporated into peptides or peptide mimetics as a phosphatase-stable phosphotyrosyl mimetic. Although Pmp has been prepared previously bearing a number of protection strategies, the N-alpha-Fmoc 4- [di-(tert-butyl)phosphonomethyl] phenylalanine form [(N alpha-Fmoc-L-Pmp('Bu-2)-OH, 3] is particularly attractive since it can be cleanly introduced into peptides using standard Fmoc protocols. Synthesis of 3 was first reported as its (D/L)-racemate, and subsequently as its L-3 enantiomer, with the latter synthesis having relied on induction of chirality using a camphor sultam auxiliary. Reported herein is an alternate enantioselective synthesis of L-3 in high ensantiomeric purity by procedures which derive the stereochemistry of the final product directly from the starting amino acid, without the need for chiral induction. A key feature of the route is the racemization-free nucleophilic substitution of lithium di-tert-butyl phosphite onto protected 4-bromomethylphenylalanine (17). (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00385-7
• 作为产物：
  描述：

  三丁基乙烯基锡 、 苄氧羰基-L-酪氨酸苄酯三氟甲烷磺酸酯 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 乙二醇二甲醚 为溶剂， 反应 2.0h， 以73%的产率得到L-N^α-benzyloxycarbonyl-4-[1-(2-ethenyl)]phenylalanine benzyl ester
  参考文献：
  名称：

  The Substrate-Activity-Screening methodology applied to receptor tyrosine kinases: A proof-of-concept study

  摘要：

  Protein kinases are widely recognized as important therapeutic targets due to their involvement in signal transduction pathways. These pathways are tightly controlled and regulated, notably by the ability of kinases to selectively phosphorylate a defined set of substrates. A wide variety of disorders can arise as a consequence of abnormal kinase-mediated phosphorylation and numerous kinase inhibitors have earned their place as key components of the modern pharmacopeia. Although "traditional" kinase inhibitors typically act by preventing the interaction between the kinase and ATP, thus stopping substrate phosphorylation, an alternative approach consists in disrupting the protein protein interaction between the kinase and its downstream partners. In order to facilitate the identification of potential chemical starting points for substrate-site inhibition approaches, we desired to investigate the application of Substrate Activity Screening to kinases. We herein report a proof-of-concept study demonstrating, on a model tyrosine kinase, that the key requirements of this methodology can be met. Namely, using peptides as model substrates, we show that a simple ADP-accumulation assay can be used to monitor substrate efficiency and that efficiency can be optimized in a modular manner. More importantly, we demonstrate that structure efficiency relationships translate into structure activity relationships upon conversion of the substrates into inhibitors. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.038

文献信息

• The Substrate-Activity-Screening methodology applied to receptor tyrosine kinases: A proof-of-concept study
  作者：Julien Chapelat、Frédéric Berst、Andreas L. Marzinzik、Henrik Moebitz、Peter Drueckes、Joerg Trappe、Doriano Fabbro、Dieter Seebach

  DOI：10.1016/j.ejmech.2012.08.038

  日期：2012.11

  Protein kinases are widely recognized as important therapeutic targets due to their involvement in signal transduction pathways. These pathways are tightly controlled and regulated, notably by the ability of kinases to selectively phosphorylate a defined set of substrates. A wide variety of disorders can arise as a consequence of abnormal kinase-mediated phosphorylation and numerous kinase inhibitors have earned their place as key components of the modern pharmacopeia. Although "traditional" kinase inhibitors typically act by preventing the interaction between the kinase and ATP, thus stopping substrate phosphorylation, an alternative approach consists in disrupting the protein protein interaction between the kinase and its downstream partners. In order to facilitate the identification of potential chemical starting points for substrate-site inhibition approaches, we desired to investigate the application of Substrate Activity Screening to kinases. We herein report a proof-of-concept study demonstrating, on a model tyrosine kinase, that the key requirements of this methodology can be met. Namely, using peptides as model substrates, we show that a simple ADP-accumulation assay can be used to monitor substrate efficiency and that efficiency can be optimized in a modular manner. More importantly, we demonstrate that structure efficiency relationships translate into structure activity relationships upon conversion of the substrates into inhibitors. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Preparation of l-Nα-Fmoc-4-[di-(tert-butyl)phosphonomethyl]phenylalanine from l-tyrosine
  作者：Zhu-Jun Yao、Yang Gao、Terrence R Burke

  DOI：10.1016/s0957-4166(99)00385-7

  日期：1999.9

  The unnatural amino acid analogue, 4-(phosphonomethyl)phenylalanine (Pmp, 2), has proven to be a valuable tool for studying protein-tyrosine kinase dependent signal transduction, where it is most often incorporated into peptides or peptide mimetics as a phosphatase-stable phosphotyrosyl mimetic. Although Pmp has been prepared previously bearing a number of protection strategies, the N-alpha-Fmoc 4- [di-(tert-butyl)phosphonomethyl] phenylalanine form [(N alpha-Fmoc-L-Pmp('Bu-2)-OH, 3] is particularly attractive since it can be cleanly introduced into peptides using standard Fmoc protocols. Synthesis of 3 was first reported as its (D/L)-racemate, and subsequently as its L-3 enantiomer, with the latter synthesis having relied on induction of chirality using a camphor sultam auxiliary. Reported herein is an alternate enantioselective synthesis of L-3 in high ensantiomeric purity by procedures which derive the stereochemistry of the final product directly from the starting amino acid, without the need for chiral induction. A key feature of the route is the racemization-free nucleophilic substitution of lithium di-tert-butyl phosphite onto protected 4-bromomethylphenylalanine (17). (C) 1999 Elsevier Science Ltd. All rights reserved.