(-)-3-deoxy-3-phenylmorphine

• 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: (-)-3-deoxy-3-phenylmorphine
• 英文别名: 3-deoxy-3-phenylmorphine；(4R,4aR,7S,7aR,12bS)-3-methyl-9-phenyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
• 化学式: C₂₃H₂₃NO₂
• 分子量: 345.441
• InChiKey: UYKTUWCMVMPLPE-GCAMRICFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-3-deoxy-3-phenylmorphine 在 甲烷磺酸 作用下， 生成 (R)-6-Methyl-10-phenyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol
  参考文献：
  名称：

  方便地合成海豚碱衍生物

  摘要：

  利用钯催化的反应的新的有效合成路线，从天然吗啡4提供（R）-11-羟基-10-甲基aporphine 2和（R）-11-羟基aporphine 3。

  DOI：

  10.1039/c39920000845
• 作为产物：
  描述：

  吗啡 、 alkaline earth salt of/the/ methylsulfuric acid 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 、 lithium chloride 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 (-)-3-deoxy-3-phenylmorphine
  参考文献：
  名称：

  方便地合成海豚碱衍生物

  摘要：

  利用钯催化的反应的新的有效合成路线，从天然吗啡4提供（R）-11-羟基-10-甲基aporphine 2和（R）-11-羟基aporphine 3。

  DOI：

  10.1039/c39920000845

文献信息

• Facile syntheses of aporphine derivatives
  作者：Martin H. Hedberg、Anette M. Johansson、Uli Hacksell

  DOI：10.1039/c39920000845

  日期：——

  New and efficient synthetic routes, utilizing palladium-catalysed reactions, provide (R)-11-hydroxy-10-methylaporphine 2 and (R)-11-hydroxyaporphine 3 from natural morphine 4.

  利用钯催化的反应的新的有效合成路线，从天然吗啡4提供（R）-11-羟基-10-甲基aporphine 2和（R）-11-羟基aporphine 3。
• 10-Substituted 11-Oxygenated (<i>R</i>)-Aporphines:  Synthesis, Pharmacology, and Modeling of 5-HT_1A Receptor Interactions
  作者：Martin H. Hedberg、Johanna M. Jansen、Gunnar Nordvall、Stephan Hjorth、Lena Unelius、Anette M. Johansson

  DOI：10.1021/jm960188q

  日期：1996.1.1

  Derivatives of the selective serotonin 5-HT1A receptor agonist (R)-11-hydroxy-10-methylaporphine (2) having various substituents in the C10-position or at the nitrogen have been synthesized from natural morphine or 6-O-acetylcodeine, respectively. The C10-substituents were introduced using efficient Stille or Suzuki cross-coupling reactions. The compounds were evaluated for their affinities to 5-HT1A and dopamine (DA) D-1 and D-2A receptors in vitro. All compounds tested displayed low (micromolar) affinities to D-1 and D-2A receptors. In addition, changes in steric bulk and/or electronic properties of the C10-substituent as compared to a C10-methyl group, as well as substitution of the N-methyl group for a hydrogen or a larger N-alkyl group, produced a marked decrease in the affinities to 5-HT1A receptors. Selected compounds that displayed moderate to high affinities to 5-HT1A receptors were evaluated for their ability to stimulate 5-HT1A receptors in vivo. The evaluated compounds behaved as agonists at 5-HT1A receptors, except for the N-propyl analogue of 2, (R)-11-hydroxy-10-methyl-N-propylnoraporphine (23), which displayed weak DA receptor agonism at the doses tested. Hence, the substitution pattern of 2 (a C10-methyl, a C11-hydroxy, and an N-methyl group) appears to be optimal for potent interaction of 10,11-disubstituted (R)-aporphines with 5-HT1A receptors. Modeling of ligand-5-HT1A receptor interactions was performed in an attempt to rationalize the observed affinity data. The binding site model suggests the presence of a ''methyl pocket'' in the 5-HT1A receptor binding site. The C11-methoxy-substituted aporphines appear to have a different binding mode compared to 2, implying a different accessibility of these compounds to the ''methyl pocket''.