2-(N-t-butyoxycarbonylamino)histamine | 950766-38-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(N-t-butyoxycarbonylamino)histamine
• 英文别名: N-Boc-2-AH；tert-butyl N-[5-(2-aminoethyl)-1H-imidazol-2-yl]carbamate
• CAS: 950766-38-8
• 化学式: C₁₀H₁₈N₄O₂
• 分子量: 226.279
• InChiKey: FGRLKQFXWKMWNB-UHFFFAOYSA-N

物化性质

• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(N-t-butyoxycarbonylamino)histamine 在 tetra(n-butyl)ammonium tribromide 、 二甲基亚砜 、 2-碘酰基苯甲酸 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 2.0h， 生成 tert-butyl [4-(5-bromo-1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrrol-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl]carbamate
  参考文献：
  名称：

  Ageladine A类似物的合成及其基质金属蛋白酶-12抑制活性。

  摘要：

  通过使用我们之前探索过的天然阿格拉定A的总合成路线，可以完成37种阿格拉定A类似物的合成。从使用新型类似物进行的基质金属蛋白酶12（MMP-12）抑制活性分析中，可以明显看出吡咯环2位上的卤素原子对于抑制活性是必不可少的，并且引入了溴原子吡咯环的4-位上的杂合对于产生有效的活性非常有效。另外，吡咯环与咪唑环的交换在增加活性方面极其有效，并且发现由此获得的类似物29显示出比天然阿格拉德汀A强约4倍的有效活性。

  DOI：

  10.1248/cpb.59.579
• 作为产物：
  描述：

  5-甲酰基-1H-咪唑-2-氨基甲酸叔丁酯 在 lithium aluminium tetrahydride 、 ammonium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 1.33h， 生成 2-(N-t-butyoxycarbonylamino)histamine
  参考文献：
  名称：

  Synthesis and matrix metalloproteinase (MMP)-12 inhibitory activity of ageladine A and its analogs

  摘要：

  Ageladine A (1) and its analogs 2-10 were expeditiously synthesized by featuring the biosynthetic route proposed for I (for 1-10) and by employing 2-(N-t-butoxycarbonylamino)imidazol-4-carbaldehyde as the starting material (for 1-8). From MMP-12 inhibitory activity assay, it appeared evident that the two bromine atoms and the three NH groups (1-NH, 14-NH, and 15-NH2) were indispensable for 1 to exhibit excellent activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.005

文献信息

• [EN] SYNTHESIS OF AGELADINE A AND ANALOGS THEREOF<br/>[FR] SYNTHÈSE D'AGÉLADINE A ET D'ANALOGUES DE CELLE-CI
  申请人：UNIV MACQUARIE

  公开号：WO2009152584A1

  公开（公告）日：2009-12-23

  The invention describes a one pot process for synthesizing a compound of structure (I), or a tautomer thereof. A compound of structure (II), or a tautomer thereof, and an aldehyde of structure RdCHO are condensed to form a condensation product. The resulting condensation product is then oxidized in the same reaction mixture to produce the compound of structure (I) or a tautomer thereof.

  该发明描述了一种一锅法合成结构式(I)化合物或其同分异构体的过程。将结构式(II)化合物或其同分异构体与RdCHO结构的醛缩合形成缩合产物。然后将所得缩合产物在同一反应混合物中氧化，以产生结构式(I)化合物或其同分异构体。
• A One-Pot Synthesis and Biological Activity of Ageladine A and Analogues
  作者：Sudhir R. Shengule、Wendy L. Loa-Kum-Cheung、Christopher R. Parish、Mélina Blairvacq、Laurent Meijer、Yoichi Nakao、Peter Karuso

  DOI：10.1021/jm200039m

  日期：2011.4.14

  A one-pot synthesis of ageladine A and analogues is reported. The key Pictet - Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition to develop the first structure-activity relationship of ageladine A analogues. One compound, which showed significant kinase activity but little MMP inhibitory activity, was found to be highly active in an antiangiogenic screen, suggesting that the angiogenic activity of ageladine A is not associated with MMP inhibition but rather kinase inhibitory activity. Cytotoxicity was excluded as a mode of action by the assay of ageladine A and an analogue against 60 human cell lines.
• A novel synthesis of the 2-amino-1H-imidazol-4-carbaldehyde derivatives and its application to the efficient synthesis of 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A
  作者：Naoki Ando、Shiro Terashima

  DOI：10.1016/j.tet.2010.05.074

  日期：2010.8

  A novel synthesis of 2-amino-1H-imidazol-4-carbaldehyde derivatives was achieved by the reaction of tert-butoxycarbonylguanidine with 3-bromo-1,1-dimethoxypropan-2-one as a key step. The usefulness of the derivatives as building blocks was proved by accomplishing the efficient synthesis of the representative 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of novel ageladine A analogs showing more potent matrix metalloproteinase (MMP)-12 inhibitory activity than the natural product
  作者：Naoki Ando、Shiro Terashima

  DOI：10.1016/j.bmcl.2009.07.099

  日期：2009.9

  By employing a previously established synthetic scheme, the synthesis described in the title was carried out in order to explore the substituent effects in the pyrrole ring of ageladine A on MMP-12 inhibitory activity. It became evident that a halogen atom (Br or Cl) at the 2-position and an additional bromine atom at the 4-position are highly effective for improving the inhibitory activity. These studies led us to discover three novel ageladine A analogs (4a. c, o) showing more potent MMP-12 inhibitory activity than the natural product. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and matrix metalloproteinase (MMP)-12 inhibitory activity of ageladine A and its analogs
  作者：Naoki Ando、Shiro Terashima

  DOI：10.1016/j.bmcl.2007.06.005

  日期：2007.8

  Ageladine A (1) and its analogs 2-10 were expeditiously synthesized by featuring the biosynthetic route proposed for I (for 1-10) and by employing 2-(N-t-butoxycarbonylamino)imidazol-4-carbaldehyde as the starting material (for 1-8). From MMP-12 inhibitory activity assay, it appeared evident that the two bromine atoms and the three NH groups (1-NH, 14-NH, and 15-NH2) were indispensable for 1 to exhibit excellent activity. (c) 2007 Elsevier Ltd. All rights reserved.