N-(t-Butoxycarbonyl)-3-(4-nitrobenzyl)-L-histidine methyl ester | 111102-61-5

• 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: N-(t-Butoxycarbonyl)-3-(4-nitrobenzyl)-L-histidine methyl ester
• 英文别名: methyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[3-[(4-nitrophenyl)methyl]imidazol-4-yl]propanoate
• CAS: 111102-61-5
• 化学式: C₁₉H₂₄N₄O₆
• 分子量: 404.423
• InChiKey: MZXLVWPZJRLGNQ-INIZCTEOSA-N

物化性质

• 沸点：
  619.3±55.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(t-Butoxycarbonyl)-3-(4-nitrobenzyl)-L-histidine methyl ester 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以93%的产率得到3-(4-Nitrobenzyl)-L-histidine dihydrochloride
  参考文献：
  名称：

  Regiospecific Synthesis of 3-Substituted L-Histidines

  摘要：

  3-取代L-组氨酸衍生物通过对N,1-双Boc-L-组氨酸甲酯进行区域特异性烷基化，使用原位生成的烷基三氟甲磺酸酯、苯基三氟甲磺酸酯和苯基亚砜酸酯制备而成。随后对N-Boc和甲酯保护基团进行酸水解，获得了一系列以双氢卤酸盐形式的修饰L-组氨酸，整体产率良好。

  DOI：

  10.1055/s-1987-27828
• 作为产物：
  描述：

  N(α)-t-butoxycarbonyl-N(τ)-triphenylmethyl-L-histidine methyl ester 在 silica gel 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 N-(t-Butoxycarbonyl)-3-(4-nitrobenzyl)-L-histidine methyl ester
  参考文献：
  名称：

  通过有效的烷基化，然后使用活化的硅胶进行脱保护，制备N（π）-烷基-组胺和组氨酸衍生物

  摘要：

  通过使用N（τ）-三苯甲基保护，实现了L-组氨酸和组胺衍生物的有效N（π）-烷基化，并且在Boc-或三苯甲基保护的存在下区域选择性去除N（τ）-三苯甲基伯胺的作用基于活化硅胶介导的0.1-0.2％三氟乙酸的温和水解。

  DOI：

  10.1016/s0040-4039(00)01792-5

文献信息

• Regiospecific Synthesis of 3-Substituted L-Histidines
  作者：John C. Hodges

  DOI：10.1055/s-1987-27828

  日期：——

  3-Substituted L-histidine derivatives were prepared by a regiospecific alkylation of N,1-bis-Boc-L-histidine methyl ester with in situ-generated alkyl triflates, benzyl triflates, and benzyl mesylates. Subsequent acid hydrolysis of N-Boc and methyl ester protecting groups afforded a variety of modified L-histidines as their dihydrohalide salts in good overall yield.

  3-取代L-组氨酸衍生物通过对N,1-双Boc-L-组氨酸甲酯进行区域特异性烷基化，使用原位生成的烷基三氟甲磺酸酯、苯基三氟甲磺酸酯和苯基亚砜酸酯制备而成。随后对N-Boc和甲酯保护基团进行酸水解，获得了一系列以双氢卤酸盐形式的修饰L-组氨酸，整体产率良好。
• Preparation of N(π)-alkyl- histamine and histidine derivatives through efficient alkylation followed by deprotection using activated silica gel
  作者：B.Moon Kim、Joon Shik Park、Jong Hyun Cho

  DOI：10.1016/s0040-4039(00)01792-5

  日期：2000.12

  Efficient N(π)-alkylation of l-histidine and histamine derivatives through employment of N(τ)-trityl-protection was achieved and regioselective removal of the N(τ)-trityl group in the presence of either Boc- or trityl-protected primary amine was effected based on a mild hydrolysis mediated by activated silica gel with 0.1–0.2% trifluoroacetic acid.

  通过使用N（τ）-三苯甲基保护，实现了L-组氨酸和组胺衍生物的有效N（π）-烷基化，并且在Boc-或三苯甲基保护的存在下区域选择性去除N（τ）-三苯甲基伯胺的作用基于活化硅胶介导的0.1-0.2％三氟乙酸的温和水解。
• Substrate-Based Design of the First Class of Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Inhibitors
  作者：Natalie A. Dales、Alexandra E. Gould、James A. Brown、Emily F. Calderwood、Bing Guan、Charles A. Minor、James M. Gavin、Paul Hales、Virendar K. Kaushik、Michael Stewart、Peter J. Tummino、Chad S. Vickers、Timothy D. Ocain、Michael A. Patane

  DOI：10.1021/ja0277226

  日期：2002.10.1

  Angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a recently identified zinc metalloprotease with carboxypeptidase activity that was identified using our genomics platform. We implemented a rational design approach to identify potent and selective ACE2 inhibitors. To this end, picomolar inhibitors of ACE2 were designed and synthesized.
• Development of targeted nanoparticles loaded with antiviral drugs for SARS-CoV-2 inhibition
  作者：Vanna Sanna、Sandro Satta、Tzung Hsiai、Mario Sechi

  DOI：10.1016/j.ejmech.2022.114121

  日期：2022.3
• Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype
  作者：C. John Blankley、John C. Hodges、Sylvester R. Klutchko、Richard J. Himmelsbach、Alexander Chucholowski、Cleo J. Connolly、Sandra J. Neergaard、Michael S. Van Nieuwenhze、Alan Sebastian

  DOI：10.1021/jm00115a014

  日期：1991.11

  Structure-activity relationships are reported for a novel class of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid derivatives that displace I-125-labeled angiotensin II from a specific subset of angiotensin II (Ang II) binding sites in rat adrenal preparations. This binding site is not the Ang II receptor mediating vascular contraction or aldosterone release, but, rather, is one whose function has not yet been fully elucidated. It has been identified in a number of tissues and has a similar affinity for Ang II and its peptide analogues as does the vascular receptor. The non-peptide compounds reported here are uniquely specific in displacing Ang II at this binding site and are inactive in antagonizing Ang II at the vascular receptor or in pharmacological assays measuring vascular effects. PD 123,319 (79), one of the most potent compounds, has an IC50 of 34 nM. Certain of these compounds may have utility in the definition and study of Ang II receptor subtypes.