Leucettamine A | 147395-95-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: Leucettamine A
• 英文别名: 4,5-bis(benzo[d][1,3]dioxol-5-ylmethyl)-1-methyl-1H-imidazol-2-amine；4,5-bis(1,3-benzodioxol-5-ylmethyl)-1-methylimidazol-2-amine
• CAS: 147395-95-7
• 化学式: C₂₀H₁₉N₃O₄
• 分子量: 365.389
• InChiKey: CHUHMZZQHYOKBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(methylamino)-1,4-bis<3,4-(methylenedioxy)phenyl>-2-butanol 在 盐酸 、 sodium hydroxide 、 重铬酸吡啶 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 Leucettamine A
  参考文献：
  名称：

  Synthesis and LTB4 receptor antagonist activities of the naturally occurring LTB4 receptor antagonist leucettamine A and related analogs

  摘要：

  The isolation and structure determination of the naturally occurring LTB4 receptor antagonist Leucettamine A (1) was recently reported.1 Herein we describe the synthesis of this natural product, the preparation of several analogues, and their effectiveness as antagonists of [H-3]LTB4 binding to intact human U-937 cells. Total synthesis of Leucettamine A 1) is achieved by a convergent route which takes advantage of the elements of symmetry within the molecule. Syntheses of analogues of 1, which lacked the same degree of symmetry, are achieved by a different approach starting from alpha-amino acids. The natural product 1 inhibits [H-3]LTB4 binding to its receptors on intact human U-937 cells with a K(i) = 3.5 +/- 0. 8 muM and is devoid of measurable agonist activity at the concentrations tested. 2-Amino imidazole analogues of 1 lacking the dioxolane groups were prepared. Generally these are significantly less potent than 1. However, one (26), designed on the basis of a putative structural overlay with LTB4, demonstrated potency comparable to that of the natural product (K(i) = 2.4 +/- 0.2 muM).

  DOI：

  10.1021/jm00074a014

文献信息

• Concise and Diversity-Oriented Route toward Polysubstituted 2-Aminoimidazole Alkaloids and Their Analogues
  作者：Denis S. Ermolat'ev、Jitender B. Bariwal、Hans P. L. Steenackers、Sigrid C. J. De Keersmaecker、Erik V. Van der Eycken

  DOI：10.1002/anie.201004256

  日期：2010.12.3

  Alkaloids of the naamine family were synthesized from diverse propargylamines in just two steps (see scheme: R1=Me, R2=substituted benzyl, R3=Ar). Thus, the addition to a propargylamine of a carbodiimide generated in situ, silver(I)‐catalyzed intramolecular hydroamidation, and subsquent deprotection provide access to the heterocyclic core of numerous natural products and biologically active compounds

  纳胺家族的生物碱仅需两个步骤就可以由多种炔丙基胺合成（参见方案：R 1 = Me，R 2 =取代的苄基，R 3 = Ar）。因此，除了在炔丙基胺中原位生成的碳二亚胺之外，银（I）催化的分子内加氢酰胺化作用以及随后的脱保护作用也使人们可以接近许多天然产物和生物活性化合物的杂环核。Boc =叔丁氧羰基，Cbz =碳苄氧基。
• Synthesis and LTB4 receptor antagonist activities of the naturally occurring LTB4 receptor antagonist leucettamine A and related analogs
  作者：Jeffrey C. Boehm、John G. Gleason、Israil Pendrak、Henry M. Sarau、Dulcie B. Schmidt、James J. Foley、William D. Kingsbury

  DOI：10.1021/jm00074a014

  日期：1993.10

  The isolation and structure determination of the naturally occurring LTB4 receptor antagonist Leucettamine A (1) was recently reported.1 Herein we describe the synthesis of this natural product, the preparation of several analogues, and their effectiveness as antagonists of [H-3]LTB4 binding to intact human U-937 cells. Total synthesis of Leucettamine A 1) is achieved by a convergent route which takes advantage of the elements of symmetry within the molecule. Syntheses of analogues of 1, which lacked the same degree of symmetry, are achieved by a different approach starting from alpha-amino acids. The natural product 1 inhibits [H-3]LTB4 binding to its receptors on intact human U-937 cells with a K(i) = 3.5 +/- 0. 8 muM and is devoid of measurable agonist activity at the concentrations tested. 2-Amino imidazole analogues of 1 lacking the dioxolane groups were prepared. Generally these are significantly less potent than 1. However, one (26), designed on the basis of a putative structural overlay with LTB4, demonstrated potency comparable to that of the natural product (K(i) = 2.4 +/- 0.2 muM).