(S)-N-(tert-butyloxycarbonyl)-4-fluoro-3-nitrophenylalanine

• 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: (S)-N-(tert-butyloxycarbonyl)-4-fluoro-3-nitrophenylalanine
• 英文别名: N-Boc-(S)-4-fluoro-3-nitrophenylalanine；L-N-Boc-4-fluoro-3-nitrophenyl alanine；L-N-Boc 4-fluoro-3-nitrophenylalanine；L-N-Boc-4-fluoro-3-nitrophenylalanine；(S)-BOC-4-Fluoro-3-nitro-phenylalanine；(2S)-3-(4-fluoro-3-nitrophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• 化学式: C₁₄H₁₇FN₂O₆
• 分子量: 328.297
• InChiKey: JKJBFOWSXXVZCU-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-N-(tert-butyloxycarbonyl)-4-fluoro-3-nitrophenylalanine 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 生成 (9S,12S)-12-[N-(tert-butyloxycarbonyl)amino]-2,11-dioxo-4-hydroxy-9-methoxycarbonyl-16-nitro-10-azatricyclo[12.2.2.1^3,7]nonadeca-3,5,7(19),14,16,17-hexaene
  参考文献：
  名称：

  Synthesis of cycloisodityrosine revisited: A selective ring forming process

  摘要：

  Cycloetherification of dipeptide (L,L) N-Boc-(4-fluoro-3-nitro)Phe-Dopa methyl ester (11) gave exclusively the (m,p)-cyclophane (14) at the expense of the 15-membered (p,p)cyclophane (16). An efficient synthesis of cycloisodityrosine was consequently developed (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(97)10664-5
• 作为产物：
  描述：

  4-氟-3-硝基溴苄 在 盐酸 、 水 、 sodium hydride 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 mineral oil 、 正戊烷 为溶剂， 反应 24.0h， 生成 (S)-N-(tert-butyloxycarbonyl)-4-fluoro-3-nitrophenylalanine
  参考文献：
  名称：

  L型氨基酸转运蛋白1（LAT1）识别的化合物设计的定量洞察

  摘要：

  L型氨基酸转运蛋白1（LAT1）是在血脑屏障（BBB）上大量表达的跨膜蛋白，可确保疏水性酸从血液向大脑的转运。由于其独特的底物特异性和在BBB的高表达，LAT1是载体介导的药物向大脑运输的引人入胜的靶标。在这项研究中，具有相当的统计质量（Q 2 = 0.53，R 2 = 0.75，Q 2  SE = 0.77，R 2  SE = 0.57）和良好的外部预测性（CCC）的比较分子场分析（CoMFA）模型= 0.91）。该模型用于指导八种新前药的合成，这些药物通过使用原位大鼠脑灌注技术测试了对LAT1的亲和力。这导致了以L-色氨酸为启动子的新型LAT1前药的创建。它还可以更好地了解靶向LAT1的高亲和力前药的分子特征，以及它们的原形和母体药物。获得的结果将有助于合理设计新型LAT1结合前药和其他与LAT1结合的化合物。

  DOI：

  10.1002/cmdc.201402281

文献信息

• Total Synthesis of Chloropeptin II (Complestatin) and Chloropeptin I
  作者：Joie Garfunkle、F. Scott Kimball、John D. Trzupek、Shinobu Takizawa、Hiroyuki Shimamura、Masaki Tomishima、Dale L. Boger

  DOI：10.1021/ja907193b

  日期：2009.11.11

  The first total synthesis of chloropeptin II (1, complestatin) is disclosed. Key elements of the approach include the use of an intramolecular Larock indole synthesis for the initial macrocyclization, adopting conditions that permit utilization of a 2-bromoaniline, incorporating a terminal alkyne substituent (-SiEt(3)) that sterically dictates the indole cyclization regioselectivity, and benefiting

  公开了氯肽素 II (1, complestatin) 的首次全合成。该方法的关键要素包括使用分子内 Larock 吲哚合成进行初始大环化，采用允许利用 2-溴苯胺的条件，结合在空间上决定吲哚环化区域选择性的末端炔烃取代基 (-SiEt(3))，并受益于苯胺保护基团 (-Ac)，该基团增强了 atropdiastereoselectivity 并减少了紧张的吲哚对后续亲电试剂的反应性。这个关键反应不仅提供了完全功能化的 1 右手环系统，转化率高 (89%) 和良好的 atropdiastereoselectivity (4:1 R:S)，而且它也代表了第一个报道的例子，它将被证明是一个有用的 Larock 大环化策略。
• Total Synthesis of Complestatin: Development of a Pd(0)-Mediated Indole Annulation for Macrocyclization
  作者：Hiroyuki Shimamura、Steven P. Breazzano、Joie Garfunkle、F. Scott Kimball、John D. Trzupek、Dale L. Boger

  DOI：10.1021/ja102304p

  日期：2010.6.9

  Full details of the initial development and continued examination of a powerful intramolecular palladium(0)-mediated indole annulation for macrocyclization closure of the strained 16-membered biaryl ring system found in complestatin (1, chloropeptin II) and the definition of factors impacting its intrinsic atropodiastereoselectivity are described. Its examination and use in an alternative, second-generation

  初步开发和继续检查强大的分子内钯 (0) 介导的吲哚环化的完整细节，用于在 complestatin (1, chloropeptin II) 中发现的应变 16 元联芳环系统的大环化闭合，以及影响其内在的因素的定义描述了 atropodiastereoselectivity。详细介绍了其在替代的第二代全合成中的检查和使用，其中大环化反应的顺序与我们的第一代全合成相反。在这种方法中，使用 ABCD 联芳醚环系统，关键的 Larock 环化是用底物 36（含有四种酚、五种仲酰胺、一种氨基甲酸酯、和四种不稳定的芳基氯化物）并提供产物 37 (56%) 仅作为具有天然 (R)-构型的单一阻转异构体（>20:1，检测限）。在这种情况下，底物的复杂性和反向大环化顺序并没有降低 atropodiastereoselectivity；相反，它提供了对 4:1 选择性的改进，在我们的第一代方法中使用类似的底物提供隔离的
• An efficient total synthesis of K-13, a non-competitive inhibitor of ACE I
  作者：Antony Bigot、Michèle Bois-Choussy、Jieping Zhu

  DOI：10.1016/s0040-4039(00)00695-x

  日期：2000.6

  An efficient synthesis of K-13, a non competitive inhibitor of ACE I, with an endo biaryl ether bond is described. The key cycloetherification reaction of linear tripeptide 10 gave 17-membered macrocycle in quantitative yield.

  描述了具有内联芳基醚键的ACE I的非竞争性抑制剂K-13的有效合成。线性三肽10的关键环醚化反应以定量收率得到17元大环。
• Total Synthesis of an Antitumor Agent RA-VII via an Efficient Preparation of Cycloisodityrosine
  作者：Antony Bigot、Marie Elise Tran Huu Dau、Jieping Zhu

  DOI：10.1021/jo990432w

  日期：1999.8.1

  Details of efficient syntheses of (9S, 12S)-cycloisodityrosine (6) and a concise total synthesis of RA-VII(1) were described. An intramolecular SNAr-based cycloetherification reaction was employed as the key ring-closure step for construction of the illusive 14-membered m,p-cyclophane. Treatment of methyl N-[N-(tert-butyloxycarbonyl)-L(3-hydroxy-4-methoxyphenylalanyl)]-L-4-fluoro-3-nitrophenylalaninate ((9S,12S)-10) with potassium carbonate in DMSO at room temperature provided a mixture of two atropdiastereomers 20a and 20b in 75% yield that were transformed into cycloisodityrosine 6 in good overall yield. Furthermore, a size-selective ring-forming process was established for methyl N-[N-(tert-butyloxycarbonyl)-L-(3,4-dihydroxyphenlalanyl)]-L-4-fluoro-3- nitrophenylalaninate ((9S,12S)-11). Thus, cyclization of 11 (K2CO3, DMSO, rt), followed by in situ methylation, gave exclusively the 14-membered m,p-cyclphane 20a and 20b without competitive formation of the alternative 15-membered p,p-cyclophane. The selective ring-forming process allowed us to develop one of the shortest and the most efficient synthesis of cycloisodityrosine to date. Computational studies have shown that it was the elimination, but not the addition, step that determined the ring-size selectivity observed in the cyclization of substrate 11. Coupling of 6 with L-N-Boc-Ala (51) proceeded efficiently to provide the corresponding tripeptide 52 that, after removal of the N-Boc function, was allowed to react with another tripeptide 53 to afford the hexapeptide 50 in good overall yield. Saponification followed by liberation of amino function from 50 gave the seco-acid, whose cyclization (DPPA, DMF, NaHCO3) afforded the natural product RA-VII (1).
• First approach to the cycloisodityrosine unit of RA-IV
  作者：Olivia Poupardin、Franck Ferreira、Jean Pierre Genet、Christine Greck

  DOI：10.1016/s0040-4039(00)02322-4

  日期：2001.2

  The syntheses of the methyl (2S,3S)-2-amino-3-(3-hydroxy-4-methoxyphenyl)-3-t-butyldimethylsilyloxypropanoate and a precursor of the cycloisodityrosine unit of RA-IV are described. (C) 2001 Elsevier Science Ltd. All rights reserved.