(8aS,9aR,10aR)-5,8,8a,9a,10,10a-hexahydro-2,3-dimethoxy-8a-(2-methylpropyl)-6H-benz[a]oxireno[g]quinolizine | 1300639-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (8aS,9aR,10aR)-5,8,8a,9a,10,10a-hexahydro-2,3-dimethoxy-8a-(2-methylpropyl)-6H-benz[a]oxireno[g]quinolizine
• 英文别名: (1R,12S,14R)-4,5-dimethoxy-12-(2-methylpropyl)-13-oxa-10-azatetracyclo[8.5.0.02,7.012,14]pentadeca-2,4,6-triene
• CAS: 1300639-86-4
• 化学式: C₁₉H₂₇NO₃
• 分子量: 317.428
• InChiKey: QWNFDBXELGMFCV-LZQZEXGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  34.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (8aS,9aR,10aR)-5,8,8a,9a,10,10a-hexahydro-2,3-dimethoxy-8a-(2-methylpropyl)-6H-benz[a]oxireno[g]quinolizine 在 dimethyl sulfide borane 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 48.5h， 以31%的产率得到(2R,3S,11bR)-1,3,4,6,7,11b-hexahydro-9,10-methoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol
  参考文献：
  名称：

  Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors

  摘要：

  Tetrabenazine (TBZ) ((+/-)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (+/-)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (K-i = 4.47 nM) was 8000-fold more potent than ()-1 (K-i = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: K-i= 3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.046
• 作为产物：
  描述：

  丁苯那嗪 在 sodium tetrahydroborate 、 高氯酸 、 五氯化磷 、 D(+)-10-樟脑磺酸 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 38.5h， 生成 (8aS,9aR,10aR)-5,8,8a,9a,10,10a-hexahydro-2,3-dimethoxy-8a-(2-methylpropyl)-6H-benz[a]oxireno[g]quinolizine
  参考文献：
  名称：

  Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors

  摘要：

  Tetrabenazine (TBZ) ((+/-)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (+/-)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (K-i = 4.47 nM) was 8000-fold more potent than ()-1 (K-i = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: K-i= 3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.046