(S)-N-Boc-3,5-二溴-4-羟基-苯丙氨酸 | 58960-71-7

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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: (S)-N-Boc-3,5-二溴-4-羟基-苯丙氨酸
• 中文别名: (S)-N-BOC-3,5-二溴-4-羟基-苯丙氨酸；Boc-3,5-二溴-L-酪氨酸
• 英文名称: N-[(1,1-dimethylethoxy)carbonyl]-3,5-dibromo-L-tyrosine
• 英文别名: N-Boc-3,5-dibromo-L-tyrosine；N-Boc-3,5-dibromotyrosine；Boc-3,4-dibromotyrosine；Boc-Tyr(3,5-diBr)-OH；Boc-3,5-dibromo-Tyr-OH；Boc-3,5-Dibromo-L-tyrosine；(2S)-3-(3,5-dibromo-4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 58960-71-7
• 化学式: C₁₄H₁₇Br₂NO₅
• mdl: MFCD00076993
• 分子量: 439.101
• InChiKey: FIKNCGRWSBGBKP-JTQLQIEISA-N

物化性质

• 熔点：
  105-108 °C
• 沸点：
  516.1±50.0 °C(Predicted)
• 密度：
  1.692±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (S)-N-Boc-3,5-二溴-4-羟基-苯丙氨酸 在 sodium tungstate (VI) dihydrate 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 potassium carbonate 、 三氟乙酸 、 zinc dibromide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 25.0h， 生成 3,5-dibromo-4-hydroxyphenylpyruvate oxime
  参考文献：
  名称：

  Syntheses of pseudoceramines A–D and a new synthesis of spermatinamine, bromotyrosine natural products from marine sponges

  摘要：

  在此，我们报告了从海洋海绵中分离出的假精胺 A-D（2â5）和精胺（1）的全合成。合成的化合物证实了所报道的结构，重要的是提供了含有两种不同溴酪氨酸结构单元的非对称精胺类天然产物。与之前报道的序列相比，我们的精胺新合成方法缩短了两个步骤，效率更高。

  DOI：

  10.1039/c1ob06722b
• 作为产物：
  描述：

  4-氨基-L-苯丙氨酸 在 Sandmeyer catalyst sodium hydroxide 、 ion-exchange resin Dowex 50 W-8 、 氢溴酸 、 溴 、 sodium nitrite 作用下， 以 水 、 溶剂黄146 、 叔丁醇 为溶剂， 反应 26.33h， 生成 (S)-N-Boc-3,5-二溴-4-羟基-苯丙氨酸
  参考文献：
  名称：

  血管紧张素II类似物。I：卤代氨基酸3-（4'-碘苯基）丙氨酸，3-（3'，5'-二溴-4'-氯苯基）丙氨酸，3-（3'，4'，5'-三溴苯基）丙氨酸和3-（2'，3'，4'，5'，6'-五溴苯基）丙氨酸†

  摘要：

  多卤代苯丙氨酸Phe（3'，4'，5'-Br 3）（3），Phe（3'，5'-Br 2 -4'-Cl）（4）和DL-Phe（2' ，（3'，4'，5'，6'-Br 5）（9）被描述。通过亲电溴化然后进行桑德迈尔反应，从Phe（4'-NH 2）立体有择地获得三卤代苯丙氨酸3和4。最疏水的氨基酸9是由五溴苄基溴和甘氨酸类似物通过相转移催化合成的。与氨基酸4,9，苯丙氨酸（4'- I）和d-PHE，[1-肌氨酸]血管紧张素II类似物（[肌氨酸产生1 [AT]用于结构活性研究和掺入tri。通过HPLC分离非对映异构五溴肽L-和D- 13。并通过催化脱卤和与[Sar 1 ] AT（10）和[Sar 1，D-Phe 8 ] AT（14）的比较进行鉴定。

  DOI：

  10.1002/hlca.19830660329

文献信息

• Studies on analgesic oligopeptides. II. Structure-activity relationship among thirty analogs of a cyclic dipeptide, cyclo(-Tyr-Arg-)
  作者：YUSUKE SASAKI、YASUYUKI AKUTSU、MICHIKO MATSUI、KENJI SUZUKI、SHINOBU SAKURADA、TAKUMI SATO、KENSUKE KISARA

  DOI：10.1248/cpb.30.4435

  日期：——

  Thirty diketopiperazines were synthesized as analogs of cyclo (-Tyr-Arg-). The analgesic activities of these analogs were evaluated after intracerebral administration in mice. In the cyclo (-X-Arg-) series of analogs, cyclo [-Tyr (Et)-Arg-] showed the most potent activity. In the cyclo (-Tyr-Y-) series of analogs, the activity decreased in the order Y=homoarginine, p-guanidinophenylalanine, 2-amino-4-guanidinobutyric acid, Lys, Orn, His, α, γ-diaminobutyric acid and Pro. Among the analogs synthesized, cyclo-[-Tyr (Et)-Har-], which was designed on the basis of the above results, exhibited remarkably potent analgesic activity, being 17 times more potent than cyclo (-Tyr-Arg-) and nearly as potent as morphine on a molar basis. The structure-activity relation of cyclo(-Tyr-Arg-) is discussed in the light of these results.

  合成了30种双吡咯并哌嗪类环(-Tyr-Arg-)类似物，并评价了它们对小鼠脑室内给药后的镇痛活性。在环(-X-Arg-)系列类似物中，环[-Tyr(Et)-Arg-]显示出最强的活性。在环(-Tyr-Y-)系列类似物中，活性按Y=高精氨酸、对胍苯丙氨酸、2-氨基-4-胍基丁酸、赖氨酸、鸟氨酸、组氨酸、α,γ-二氨基丁酸和脯氨酸的顺序递减。在合成的类似物中，环-[-Tyr(Et)-Har-]基于上述结果设计，表现出极其强大的镇痛活性，比环(-Tyr-Arg-)强17倍，按摩尔计算几乎与吗啡一样有效。根据这些结果，讨论了环(-Tyr-Arg-)的构效关系。
• An efficient synthesis of l-3,4,5-trioxygenated phenylalanine compounds from l-tyrosine
  作者：Ruijiao Chen、Hao Liu、Xiubing Liu、Xiaochuan Chen

  DOI：10.1016/j.tet.2013.02.079

  日期：2013.4

  A new strategy for the synthesis of l-3,4,5-trioxygenated phenylalanine derivatives from l-tyrosine is developed for the first time. The approach, featuring the transformation of aryl diiodide to bis-phenol via a one-pot procedure including lithiation, boronation, and oxidation, is highly practical. By this robust protocol, N-protected l-3,5-bis(tert-butyldimethylsilyloxy)-4-methoxy-phenylalanine and

  用于合成的新策略升-3,4,5- trioxygenated从苯丙氨酸衍生物升-酪氨酸被首次开发的。这种方法的特点是通过一锅法（包括锂化，硼化和氧化）将芳基二碘化物转化为双酚，这种方法非常实用。通过该稳健的方案，由N-保护的l -3,5-双（叔丁基二甲基甲硅烷氧基）-4-甲氧基-苯丙氨酸和l -3,4,5-三甲氧基-苯丙氨酸衍生物在9步中用36步从l-酪氨酸获得–40％的整体收益率。
• Development of Human Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists. 1. Potent and Selective Small Molecule CGRP Antagonists. 1-[<i>N</i>²-[3,5-Dibromo-<i>N</i>-[[4-(3,4-dihydro-2(1<i>H</i>)-oxoquinazolin-3-yl)-1- piperidinyl]carbonyl]-<scp>d</scp>-tyrosyl]-<scp>l</scp>-lysyl]-4-(4-pyridinyl)piperazine:  The First CGRP Antagonist for Clinical Trials in Acute Migraine
  作者：Klaus Rudolf、Wolfgang Eberlein、Wolfhard Engel、Helmut Pieper、Michael Entzeroth、Gerhard Hallermayer、Henri Doods

  DOI：10.1021/jm0490641

  日期：2005.9.1

  Although the triptans have greatly improved the acute treatment of migraine headache, there are yet many shortcomings. Therefore, new strategies for the treatment of migraine are needed which offer advantages over current therapy, e.g. triptans. Our novel approach was based on the hypothesis that the release of calcitonin gene-related peptide (CGRP) could play a causative role in migraine headache. Thus we initiated a program aimed at the design and synthesis of small molecule CGRP receptor antagonists. High throughput screening led to the identification of (R)-Tyr-(S)-Lys dipeptide-like compounds that showed weak but unequivocal binding to the human CGRP receptor. Lead optimization afforded highly potent CGRP antagonists, the prototype being compound 19 (BIBN4096). This compound exhibiting a favorable biological profile was selected for initial clinical trials. A proof of concept study indicated that intravenous application of 19 was effective in the treatment of acute migraine headache. This finding strongly supports our initial working hypothesis that CGRP plays an important role in the pathophysiology of migraine.
• The synthesis, distribution, and anti-hepatic cancer activity of YSL
  作者：Wenfeng Ding、Jiali Zhang、Zhi Yao、Rong Lu、Dezhu Wu、Ginfu Li、Zilong Shen、Yingji Sun、Gang Lin、Chao Wang、Ming Zhao、Shiqi Peng

  DOI：10.1016/j.bmc.2004.06.030

  日期：2004.9

  YSL was prepared stepwise from C terminal to N terminal with the side chain un-protective amino acids, Boc-Leu-OMe, Boc-Ser-OH, and Boc-Tyr-OH, as the starting materials in 39.5% total yield (31.2g/per batch). With the side chain un-protective Boc-(3,5-dibromo)-Tyr-OH and HCl.Ser-Leu-OMe as the starting materials (3,5-H-3-Tyr)-Ser-Leu-OH was obtained in 29% yield. The determination of radioactive quantity in the urine and feces indicated that even after the administration for [30h only 8.4% (5.35% in urine and 3.05% in feces) of total radioactive quantity from the metabolite of [3,5-H-3-Tyr]-Ser-Leu-OH were monitored. The distribution study revealed the relative accumulation level of the individual tissue was arranged in the sequence of spleen > liver > kidney > lung > heart > muscle > brain. Selecting hepatic cancer as the target YSL significantly increased the survival time of H22 tumor cells implanted mice. (C) 2004 Elsevier Ltd. All rights reserved.
• Characterization of thyroid hormone receptor α (TRα)-specific analogs with varying inner- and outer-ring substituents
  作者：Cory A. Ocasio、Thomas S. Scanlan

  DOI：10.1016/j.bmc.2007.10.040

  日期：2008.1

  Analogs of the TR alpha-specific thyromimetic CO23 were synthesized and analyzed in vitro using competitive binding and transactivation assays. Like CO23, all analogs bind to both thyroid hormone receptor subtypes with about the same affinity; however, modification of CO23 by derivatization of the 3' position of the outer-ring or replacement of the inner-ring iodides with bromides attenuates binding. Despite lacking a preference in binding to TR alpha, all analogs display TR alpha-specificity in transactivation assays using U2OS and HeLa cells. At best, several agonists exhibit an approximately 6-12-fold preference in transactivation when tested with TR alpha in HeLa cells. One analog, CO24, showed in vivo TR alpha-specific action in a tadpole metamorphosis assay. (c) 2007 Elsevier Ltd. All rights reserved.