methyl (4R,4aR,7R,7aR,12bS,14S)-7,9-dimethoxy-3,14-dimethyl-1,2,3,4,7,7a-hexahydro-7,4a-ethano-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carboxylate | 227453-21-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: methyl (4R,4aR,7R,7aR,12bS,14S)-7,9-dimethoxy-3,14-dimethyl-1,2,3,4,7,7a-hexahydro-7,4a-ethano-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carboxylate
• CAS: 227453-21-6
• 化学式: C₂₄H₂₉NO₅
• 分子量: 411.498
• InChiKey: CZCREWKJKQMKIT-OFFIMBHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  30.0
• 可旋转键数：
  3.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  57.23
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl (4R,4aR,7R,7aR,12bS,14S)-7,9-dimethoxy-3,14-dimethyl-1,2,3,4,7,7a-hexahydro-7,4a-ethano-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carboxylate 在 氢氧化钾 作用下， 以 乙醚 、 乙二醇 为溶剂， 反应 7.25h， 生成 (-)-4,5α-epoxy-7α,18-(epoxymethano)-6-methoxy-7β,17,21,21-tetramethyl-6α,14α-ethenoisomorphinan-3-ol
  参考文献：
  名称：

  chemistry of opium alkaloids. part 44: Synthesis and opioid receptor binding profile of substituted ethenoisomorphinans and ethenomorphinans 1Part XLIII. Baas, J. M. A.; Woudenberg, R. H.; Maat, L. Liebigs Ann./Recueil 1997, 13. 1

  摘要：

  7- And 8-substituted 6 alpha,14 alpha-ethenoisomorphinans were synthesized by reaction of properly substituted morpkinan-6,8-dienes (analogues of thebaine) with methyl vinyl ketone or ethyl acrylate. Reaction with the appropriate Grignard reagent gave the 7- and 8-dialkylmethanols, respectively. Cleavage of the 3-methyl ether with KOH/glycol or boron tribromide afforded the 3-hydroxyl derivatives. In general, the compounds with the ethoxycarbonyl or dimethylmethanol substituent at the 8 alpha-position showed lower affinity for the mu, kappa, and delta opioid receptor subtypes than the corresponding 7 alpha- and 7 beta-substituted compounds. Introduction of a chloro substituent in position 18 increased the potency significantly. The 7-substituent could be connected to the 18-position without loss of affinity. 5 beta-alkyl substitution of 6 alpha, 14 alpha-ethenoisomorphinans led to a decrease in affinity for the three opioid receptor subtypes. In the 5 beta-methyl series the affinity for the mu and delta receptors increased from 7 alpha-dimethylmethanol to 7 alpha-methylhexylmethanol. In the 5 beta-alkyl series, the affinity for the mu-receptor could be increased by connecting the 5- and 7-substituents, yielding a compound with high mu-selectivity. The new 6 beta,14 beta-ethenomorphinans did not show affinity for any of the opioid receptors, in accordance with the inactivity earlier found in in vivo experiments. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00267-3
• 作为产物：
  描述：

  蒂巴因 、 甲基丙烯酸甲酯 生成 methyl (4R,4aR,7R,7aR,12bS,14S)-7,9-dimethoxy-3,14-dimethyl-1,2,3,4,7,7a-hexahydro-7,4a-ethano-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carboxylate
  参考文献：
  名称：

  chemistry of opium alkaloids. part 44: Synthesis and opioid receptor binding profile of substituted ethenoisomorphinans and ethenomorphinans 1Part XLIII. Baas, J. M. A.; Woudenberg, R. H.; Maat, L. Liebigs Ann./Recueil 1997, 13. 1

  摘要：

  7- And 8-substituted 6 alpha,14 alpha-ethenoisomorphinans were synthesized by reaction of properly substituted morpkinan-6,8-dienes (analogues of thebaine) with methyl vinyl ketone or ethyl acrylate. Reaction with the appropriate Grignard reagent gave the 7- and 8-dialkylmethanols, respectively. Cleavage of the 3-methyl ether with KOH/glycol or boron tribromide afforded the 3-hydroxyl derivatives. In general, the compounds with the ethoxycarbonyl or dimethylmethanol substituent at the 8 alpha-position showed lower affinity for the mu, kappa, and delta opioid receptor subtypes than the corresponding 7 alpha- and 7 beta-substituted compounds. Introduction of a chloro substituent in position 18 increased the potency significantly. The 7-substituent could be connected to the 18-position without loss of affinity. 5 beta-alkyl substitution of 6 alpha, 14 alpha-ethenoisomorphinans led to a decrease in affinity for the three opioid receptor subtypes. In the 5 beta-methyl series the affinity for the mu and delta receptors increased from 7 alpha-dimethylmethanol to 7 alpha-methylhexylmethanol. In the 5 beta-alkyl series, the affinity for the mu-receptor could be increased by connecting the 5- and 7-substituents, yielding a compound with high mu-selectivity. The new 6 beta,14 beta-ethenomorphinans did not show affinity for any of the opioid receptors, in accordance with the inactivity earlier found in in vivo experiments. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00267-3