1,4-二氧杂-8-氮杂螺[4.5]癸烷-6,8-二羧酸,7-丁基-6-甲基-,6-甲基8-(苯基甲基)酯 | 135967-41-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 中文名称: 1,4-二氧杂-8-氮杂螺[4.5]癸烷-6,8-二羧酸,7-丁基-6-甲基-,6-甲基8-(苯基甲基)酯
• 英文名称: 2-n-butyl-1-(carbobenzyloxy)-3-carbomethoxy-3-methyl-4-piperidone ethylene ketal
• 英文别名: 8-O-benzyl 6-O-methyl 7-butyl-6-methyl-1,4-dioxa-8-azaspiro[4.5]decane-6,8-dicarboxylate
• CAS: 135967-41-8
• 化学式: C₂₂H₃₁NO₆
• 分子量: 405.491
• InChiKey: NBTGOBDOPXLUOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  74.3
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1,4-二氧杂-8-氮杂螺[4.5]癸烷-6,8-二羧酸,7-丁基-6-甲基-,6-甲基8-(苯基甲基)酯 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以88%的产率得到2-n-butyl-1,3-dimethyl-3-(hydroxymethyl)-4-piperidone ethylene ketal
  参考文献：
  名称：

  Synthesis of inhibitors of 2,3-oxidosqualene-lanosterol cyclase: conjugate addition of organocuprates to N-(carbobenzyloxy)-3-carbomethoxy-5,6-dihydro-4-pyridone.

  摘要：

  Synthesis of ammonium ion analogues of the first cationic intermediate, 5, presumed to be formed during the cyclization of 2,3-oxidosqualene by 2,3-oxidosqualene-lanosterol cyclase are reported. The required 2,3-substituted-4-piperidinols are prepared by conjugate addition of higher order alkyl (2-thienyl)(cyano)cuprates to 1-(carbobenzyloxy)-3-carbomethoxy-5,6-dihydro-4-pyridone. The nitrogen protecting group (carbobenzyloxy) is key to the synthesis in that it allows the conjugate addition to proceed in high yield and is easily converted to the required N-methyl group in the final products. The key terpenoid side chain appended to C-2 of the piperidinols was constructed from homofarnesyl bromide and 1,5-difunctionalized homoisopentenyl derivatives prepared by zirconium-catalyzed carboalumination of protected 1-butyn-4-ol.

  DOI：

  10.1021/jo00036a008
• 作为产物：
  描述：

  4-氧代-1,3-哌啶二羧酸 3-甲基 1-(苯基甲基)酯 在 双氧水 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 75.0h， 生成 1,4-二氧杂-8-氮杂螺[4.5]癸烷-6,8-二羧酸,7-丁基-6-甲基-,6-甲基8-(苯基甲基)酯
  参考文献：
  名称：

  Synthesis of inhibitors of 2,3-oxidosqualene-lanosterol cyclase: conjugate addition of organocuprates to N-(carbobenzyloxy)-3-carbomethoxy-5,6-dihydro-4-pyridone.

  摘要：

  Synthesis of ammonium ion analogues of the first cationic intermediate, 5, presumed to be formed during the cyclization of 2,3-oxidosqualene by 2,3-oxidosqualene-lanosterol cyclase are reported. The required 2,3-substituted-4-piperidinols are prepared by conjugate addition of higher order alkyl (2-thienyl)(cyano)cuprates to 1-(carbobenzyloxy)-3-carbomethoxy-5,6-dihydro-4-pyridone. The nitrogen protecting group (carbobenzyloxy) is key to the synthesis in that it allows the conjugate addition to proceed in high yield and is easily converted to the required N-methyl group in the final products. The key terpenoid side chain appended to C-2 of the piperidinols was constructed from homofarnesyl bromide and 1,5-difunctionalized homoisopentenyl derivatives prepared by zirconium-catalyzed carboalumination of protected 1-butyn-4-ol.

  DOI：

  10.1021/jo00036a008

文献信息

• Efficient route to the synthesis of C-2, C-3 substituted 4-piperidones
  作者：Dharmpal S. Dodd、Allan C. Oehlschlager

  DOI：10.1016/s0040-4039(00)79755-3

  日期：1991.7

  6-dihydro-4-pyridone ((1) has proven to be exceptionally receptive in the conjugate addition of organocuprates to give C-2 substituted piperidones having the C-3 position activated toward alkylation. Enone (1) was used as the key synthon in the synthesis of C-1, C-2 and C-3 substituted 4-piperidinol (8).

  1-Carbobenzoxy-3-carbomethoxy-5,6-dihydro-4-pyridone（（1））已被证明在共轭添加有机铜酸盐时产生了C-3取代的C-2取代的哌啶酮，C-3位置朝着烷基化方向活化。烯酮（1）被用作合成C-1，C-2和C-3取代的4-哌啶醇的关键合成子（8）。