苄氧羰基-L-酪氨酸苄酯三氟甲烷磺酸酯 | 183070-41-9

• 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: 苄氧羰基-L-酪氨酸苄酯三氟甲烷磺酸酯
• 英文名称: L-N^α-Cbz-4-(O-trifluoromethanesulfonate)tyrosine benzyl ester
• 英文别名: Cbz-Tyr(Tf)-Bzl；Cbz-L-Tyrosine benzyl ester triflate；benzyl (2S)-2-(phenylmethoxycarbonylamino)-3-[4-(trifluoromethylsulfonyloxy)phenyl]propanoate
• CAS: 183070-41-9
• 化学式: C₂₅H₂₂F₃NO₇S
• 分子量: 537.513
• InChiKey: CVDJKKOIYOSXFZ-QFIPXVFZSA-N

物化性质

• 沸点：
  648.5±55.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  苄氧羰基-L-酪氨酸苄酯三氟甲烷磺酸酯 在 palladium diacetate 、 palladium on activated charcoal 1,1'-双(二苯基膦)二茂铁 、 三氟化硼乙醚 、 氢气 、 potassium acetate 、 sodium carbonate 作用下， 以 二氯甲烷 、 环己烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 8.0h， 生成 FMOC-p-羧基-Phe(OtBu)-OH
  参考文献：
  名称：

  用于基于Fmoc的固相肽合成的4-羧基苯丙氨酸及其衍生物的立体定向合成

  摘要：

  获得N α -苄氧羰基-L-酪氨酸（ø -三氟甲基）苄基酯，我们准备了使用钯（0）催化的羰基化反应对映体纯的4- carboxyphenylalanine和4- methoxycarbonylphenylalanine衍生物。这些非天然氨基酸被适当地保护，并用于使用Fmoc /叔丁基方法的固相肽合成中。

  DOI：

  10.1016/s0040-4039(96)01490-6
• 作为产物：
  描述：

  N-苄氧羰基-L-酪氨酸 在 2,6-二甲基吡啶 、 caesium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 苄氧羰基-L-酪氨酸苄酯三氟甲烷磺酸酯
  参考文献：
  名称：

  用于基于Fmoc的固相肽合成的4-羧基苯丙氨酸及其衍生物的立体定向合成

  摘要：

  获得N α -苄氧羰基-L-酪氨酸（ø -三氟甲基）苄基酯，我们准备了使用钯（0）催化的羰基化反应对映体纯的4- carboxyphenylalanine和4- methoxycarbonylphenylalanine衍生物。这些非天然氨基酸被适当地保护，并用于使用Fmoc /叔丁基方法的固相肽合成中。

  DOI：

  10.1016/s0040-4039(96)01490-6

文献信息

• A Practical Method for the Synthesis of Enantiomerically Pure 4-Borono-<b>L</b>-phenylalanine
  作者：Hiroyuki Nakamura、Masaru Fujiwara、Yoshinori Yamamoto

  DOI：10.1246/bcsj.73.231

  日期：2000.1

  Enantiomerically pure L-BPA (4-borono-L-phenylalanine) was synthesized from L-tyrosine or 4-iodo-L-phenylalanine derivatives using the palladium-catalyzed cross-coupling reaction of pinacolborane (2,3-dimethyl-2,3-butanediolatoboron). Cbz-Tyr(Nf)-OBzl (2b) underwent the cross-coupling reaction with pinacolborane (1) in the presence of [PdCl2(PPh3)2] catalyst to give N-benzyloxycarbonyl-4-(2,3-dimethyl-2,3-butanediolatoboryl)-L-phenylalanine benzyl ester (3a) in 58% yield. The reaction of the 4-iodo-L-phenylalanine derivatives, such as N-benzyloxycarbonyl-4-iodo-L-phenylalanine benzyl ester (2c), N,N-dibenzyl-4-iodo-L-phenylalanine benzyl ester (2d), (4S)-3-benzyloxycarbonyl-4-(4-iodobenzyl)-5-oxazolidinone (2e), and (4S)-3-t-butyloxycarbonyl-4-(4-iodobenzyl)-5-oxazolidinone (2f), with 1 proceeded very smoothly in the presence of [PdCl2(dppf)] catalyst, giving N-benzyloxycarbonyl-4-(2,3-dimethyl-2,3-butanediolatoboryl)-L-phenylalanine benzyl ester (3a), N,N-dibenzyl-4-(2,3-dimethyl-2,3-butanediolatoboryl)-L-phenylalanine benzyl ester (3b), (4S)-3-benzyloxycarbonyl-4-[4-(2,3-dimethyl-2,3-butanediolatoboryl)benzyl]-5-oxazolidinone (3c), and (4S)-3-butyloxycarbonyl-4-[4-(2,3-dimethyl-2,3-butanediolatoboryl)benzyl]-5-oxazolidinone (3d), respectively, in high yields. Deprotection of 3a—d gave enantiomerically pure L-BPA in high total yields.

  利用钯催化的频哪醇硼烷（2,3-二甲基-2,3-丁二醇硼）交叉偶联反应，从 L-酪氨酸或 4-碘-L-苯丙氨酸衍生物合成了对映体纯度极高的 L-BPA（4-硼-L-苯丙氨酸）。在[PdCl2(PPh3)2]催化剂存在下，Cbz-Tyr(Nf)-OBzl (2b) 与频哪醇硼烷 (1) 发生交叉偶联反应，得到 N-苄氧羰基-4-(2,3-二甲基-2,3-丁二醇基)-L-苯丙氨酸苄酯 (3a)，收率为 58%。4-碘-L-苯丙氨酸衍生物的反应，如 N-苄氧羰基-4-碘-L-苯丙氨酸苄酯 (2c)、N,N-二苄基-4-碘-L-苯丙氨酸苄酯 (2d)、(4S)-3-苄氧羰基-4-(4-碘苄基)-5-恶唑烷酮(2e)和(4S)-3-叔丁氧羰基-4-(4-碘苄基)-5-恶唑烷酮(2f)，其中 1 在[PdCl2(dppf)]催化剂存在下进行得非常顺利、得到 N-苄氧羰基-4-(2,3-二甲基-2,3-丁二醇二硼酸基)-L-苯丙氨酸苄酯 (3a)、N,N-二苄基-4-(2,3-二甲基-2,3-丁二醇二硼酸基)-L-苯丙氨酸苄酯 (3b)、(4S)-3-苄氧羰基-4-[4-(2、3-(2,3-二甲基-2,3-丁二醇基)苄基]-5-恶唑烷酮 (3c) 和 (4S)-3-丁酰氧羰基-4-[4-(2,3-二甲基-2,3-丁二醇基)苄基]-5-恶唑烷酮 (3d)。对 3a-d 进行脱保护处理后，可得到对映体纯度很高的 L-BPA，总产率也很高。
• Synthesis of novel L-phenylalanine derivatives substituted with a keto ylide as stable precursor of a vicinal tricarbonyl moiety
  作者：Heinz Fretz

  DOI：10.1016/0040-4039(96)01978-8

  日期：1996.11

  Novel L-phenylalanine derivatives 5 containing a vicinal tricarbonyl moiety at the para position of the phenyl ring were prepared in 4 steps starting from Nα-Cbz-L-tyrosine benzyl ester. A 7 step reaction sequence lead to Nα-Fmoc protected derivatives 9 with the tricarbonyl structure masked as its stable keto ylide precursor, which is suitable for solid phase peptide synthesis. The phosphoranylidene

  新颖的L-苯丙氨酸衍生物5在苯基环的对位含有邻位三羰基部分在制备4个选自N开始步骤α -Cbz -L-酪氨酸苄酯。A 7步骤反应顺序导致Ñ α -Fmoc保护的衍生物9与掩蔽为它的稳定的酮前体叶立德，其适合于固相肽合成的三羰基结构。的正膦基亚基中间体8转化到三氧代化合物5与过硫酸氢钾®作为氧化剂
• 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.
• A Concise Synthesis of Enantiomerically Pure <scp>l</scp>-(4-Boronophenyl)alanine from <scp>l</scp>-Tyrosine
  作者：Hiroyuki Nakamura、Masaru Fujiwara、Yoshinori Yamamoto

  DOI：10.1021/jo980818r

  日期：1998.10.1
• 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.