methyl 3-<4-(benzenesulfonylamino)butyl>-6-(1-hydroxyethyl-1-methyl)azulene-1-carboxylate | 150094-22-7

• 分子结构分类: 有机化合物 - 碳氢化合物 - 不饱和烃
• 英文名称: methyl 3-<4-(benzenesulfonylamino)butyl>-6-(1-hydroxyethyl-1-methyl)azulene-1-carboxylate
• 英文别名: Methyl 3-[4-(benzenesulfonamido)butyl]-6-(2-hydroxypropan-2-yl)azulene-1-carboxylate
• CAS: 150094-22-7
• 化学式: C₂₅H₂₉NO₅S
• 分子量: 455.575
• InChiKey: QINIKTJFNJDKIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-<4-(benzenesulfonylamino)butyl>-6-(1-hydroxyethyl-1-methyl)azulene-1-carboxylate 在 sodium hydroxide 、 硼烷四氢呋喃络合物 、 磷酸 、 双氧水 、 对甲苯磺酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 6.5h， 生成 N-(4-{6-[2-(tert-Butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-azulen-1-yl}-butyl)-benzenesulfonamide
  参考文献：
  名称：

  Azulene derivatives as TXA2/PGH2 receptor antagonists—II. Synthesis and biological activity of 6-mono- and 6-dihydroxylated-isopropylazulenes

  摘要：

  In order to examine the correlation between activity and hydrophilicity of the side chain of sodium 3-[4-(4-chlorobenzenesulfonylamino)butyl]-6-isopropylazulene-1-sulfonate (KT2-962), a non-prostanoid TXA(2)/PGH(2) receptor antagonist, one or two hydroxyl groups were introduced into the isopropyl moiety. A series of 6-hydroxylated-isopropylazulenes were synthesized by regioselective oxidation of 6-isopropylazulenes and their in vitro and in vivo antagonistic activities were studied. Both the primary and tertiary alcohols, monohydroxylated derivatives, exhibited potent biological activities comparable to unmodified 6-isopropylazulenes both in vitro and in vivo. In contrast, the activities of 1,2- and 1,3-diols of 6-substituted derivatives, markedly decreased, but recovered by O-isopropylidenation of the dihydroxyl moiety. These findings indicate that the moderate hydrophobicity of substituent at the 6-position of the azulene ring might be required for the activity and the size of the substituent at this position, not so rigid for keeping potent biological activity. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00038-7
• 作为产物：
  描述：

  methyl 3-<4-<(phenylsulfonyl)amino>butyl>-6-isopropylazulene-1-carboxylate 在 氧气 、 potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以66%的产率得到methyl 3-<4-(benzenesulfonylamino)butyl>-6-(1-hydroxyethyl-1-methyl)azulene-1-carboxylate
  参考文献：
  名称：

  Simple and Selective Oxidation of 6-Alkylazulene Derivatives

  摘要：

  描述了在薁环 1 位具有吸电子取代基的 6-烷基薁衍生物的简单和区域选择性氧化。分子氧的氧化在乙酸钾 (KOAc) 或氢氧化四丁基铵 (Bu4NOH) 等碱存在下顺利进行，并且似乎是通过甘菊环衍生物的烯醇化进行的。 6-异丙基薁衍生物的氧化得到叔醇，该叔醇很容易转化为伯醇。 6-甲基薁衍生物的氧化提供了薁-6-羧酸酯衍生物，但通过氧化6-甲基薁-1-甲酸甲酯而获得的二甲基薁-1,6-二羧酸酯被发现在6-位被选择性还原。硼氢化钠（NaBH4）的位置。相比之下，1,6-二甲酸二甲酯与无水磷酸（100%PA）在1位选择性地进行脱甲氧基羰基化，得到6-甲酸甲酯。通过氧化 6-烷基甘菊环得到的那些化合物是进一步修饰甘菊环 6 位侧链的有用的关键中间体。

  DOI：

  10.1055/s-1994-25706

文献信息

• Simple and Selective Oxidation of 6-Alkylazulene Derivatives
  作者：Masayuki Yokota、Rei Koyama、Hiromi Hayashi、Satoko Uchibori、Tsuyoshi Tomiyama、Hiroshi Miyazaki

  DOI：10.1055/s-1994-25706

  日期：——

  The simple and regioseletive oxidation of 6-alkylazulene derivatives with an electron-withdrawing substituent at the 1-position of the azulene ring is described. Oxidation with molecular oxygen proceeds smoothly in the presence of a base such as potassium acetate (KOAc) or tetrabutylammonium hydroxide (Bu4NOH), and appears to proceed via enolization of the azulene derivatives. Oxidation of 6-isopropylazulene derivatives gave tertiary alcohols, which were easily converted to primary alcohols. Oxidation of 6-methylazulene derivatives provided azulene-6-carboxylate derivatives but dimethhyl azulene-1,6-dicarboxylate, which had been obtained by the oxidation of methyl 6-methylazulene-1-carboxylate, was found to be reduced selectively at the 6-position by sodium borohydride (NaBH4). In contrast, demethoxycarbonylation of dimethyl azulene-1,6-di-carboxylate with anhydrous phosphoric acid (100%PA) proceeded selectively at the 1-position to give methyl azulene-6-carboxylate. Those compounds obtained by the oxidation of 6-alkylazulenes are useful key intermediates for further modifications of the side chains at the 6-position of azulenes.

  描述了在薁环 1 位具有吸电子取代基的 6-烷基薁衍生物的简单和区域选择性氧化。分子氧的氧化在乙酸钾 (KOAc) 或氢氧化四丁基铵 (Bu4NOH) 等碱存在下顺利进行，并且似乎是通过甘菊环衍生物的烯醇化进行的。 6-异丙基薁衍生物的氧化得到叔醇，该叔醇很容易转化为伯醇。 6-甲基薁衍生物的氧化提供了薁-6-羧酸酯衍生物，但通过氧化6-甲基薁-1-甲酸甲酯而获得的二甲基薁-1,6-二羧酸酯被发现在6-位被选择性还原。硼氢化钠（NaBH4）的位置。相比之下，1,6-二甲酸二甲酯与无水磷酸（100%PA）在1位选择性地进行脱甲氧基羰基化，得到6-甲酸甲酯。通过氧化 6-烷基甘菊环得到的那些化合物是进一步修饰甘菊环 6 位侧链的有用的关键中间体。
• Azulene derivatives as TXA2/PGH2 receptor antagonists—II. Synthesis and biological activity of 6-mono- and 6-dihydroxylated-isopropylazulenes
  作者：Masayuki Yokota、Satoko Uchibori、Hiromi Hayashi、Rei Koyama、Kazuhiro Kosakai、Shuichi Wakabayashi、Tsuyoshi Tomiyama

  DOI：10.1016/0968-0896(96)00038-7

  日期：1996.4

  In order to examine the correlation between activity and hydrophilicity of the side chain of sodium 3-[4-(4-chlorobenzenesulfonylamino)butyl]-6-isopropylazulene-1-sulfonate (KT2-962), a non-prostanoid TXA(2)/PGH(2) receptor antagonist, one or two hydroxyl groups were introduced into the isopropyl moiety. A series of 6-hydroxylated-isopropylazulenes were synthesized by regioselective oxidation of 6-isopropylazulenes and their in vitro and in vivo antagonistic activities were studied. Both the primary and tertiary alcohols, monohydroxylated derivatives, exhibited potent biological activities comparable to unmodified 6-isopropylazulenes both in vitro and in vivo. In contrast, the activities of 1,2- and 1,3-diols of 6-substituted derivatives, markedly decreased, but recovered by O-isopropylidenation of the dihydroxyl moiety. These findings indicate that the moderate hydrophobicity of substituent at the 6-position of the azulene ring might be required for the activity and the size of the substituent at this position, not so rigid for keeping potent biological activity. Copyright (C) 1996 Elsevier Science Ltd