5β-benzyl-4,5α-epoxy-3-methoxy-17-methyl-6,7,8,14-tetrahydro-morphinan | 1039687-36-9

• 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: 5β-benzyl-4,5α-epoxy-3-methoxy-17-methyl-6,7,8,14-tetrahydro-morphinan
• 英文别名: 5β-benzyl-6-demethoxythebaine
• CAS: 1039687-36-9
• 化学式: C₂₅H₂₅NO₂
• 分子量: 371.479
• InChiKey: PIVSFEVOFLJRGI-ZPZUNKDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.06
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  21.7
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5β-benzyl-4,5α-epoxy-3-methoxy-17-methyl-6,7,8,14-tetrahydro-morphinan 在 甲烷磺酸 、 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 1-benzylapomorphine
  参考文献：
  名称：

  1-substituted apomorphines as potent dopamine agonists

  摘要：

  A novel set of 1-substituted apomorphines as dopaminergic agonists were synthesized according to our new strategy employing the acid-catalyzed rearrangement of diversely functionalized 5 beta-substituted-6-demethoxythebaines. The activities of new compounds for dopamine receptors subtypes were evaluated using HEK293 based stable cell lines expressing D-1, D-2L or D-3 receptor subtypes. All studied compounds had affinities in nanomolar range for D-2L and D-3 receptors and the change of the nature of substituent in position 1 had only moderate effect. D-1 receptors were sensitive to the introduction of the 4-OH-benzyl function resulting in an increased affinity. The small hydrophilic group (hydroxymethyl) highly reduced the agonist affinity and potency thereby increasing subtype selectivity. This strategy for selective modulation of affinities and potencies of 1-substituted apomorphines gives essential hints for future design of subtype selective dopaminergic ligands. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.014
• 作为产物：
  描述：

  6-O-mesylneopine 在 四丁基氟化铵 、 叔丁基锂 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 5.5h， 生成 5β-benzyl-4,5α-epoxy-3-methoxy-17-methyl-6,7,8,14-tetrahydro-morphinan
  参考文献：
  名称：

  1-substituted apomorphines as potent dopamine agonists

  摘要：

  A novel set of 1-substituted apomorphines as dopaminergic agonists were synthesized according to our new strategy employing the acid-catalyzed rearrangement of diversely functionalized 5 beta-substituted-6-demethoxythebaines. The activities of new compounds for dopamine receptors subtypes were evaluated using HEK293 based stable cell lines expressing D-1, D-2L or D-3 receptor subtypes. All studied compounds had affinities in nanomolar range for D-2L and D-3 receptors and the change of the nature of substituent in position 1 had only moderate effect. D-1 receptors were sensitive to the introduction of the 4-OH-benzyl function resulting in an increased affinity. The small hydrophilic group (hydroxymethyl) highly reduced the agonist affinity and potency thereby increasing subtype selectivity. This strategy for selective modulation of affinities and potencies of 1-substituted apomorphines gives essential hints for future design of subtype selective dopaminergic ligands. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.014

文献信息

• Benzylation of morphinandienes and new aspects of their acid-catalyzed rearrangement to new aporphines
  作者：Attila Sipos、Sándor Berényi

  DOI：10.1016/j.tet.2008.04.069

  日期：2008.6

  5β- versus 7-benzyl products and the deviation of the electronic structure of ring C of 7-benzyl products. The acid-catalyzed rearrangement of morphinan-5,8-dienes, 5,6- and 6,7-disubstituted morphinan-6,8-dienes was achieved and mechanistic interpretations for the formation of new, potentially dopamine-active aporphines were provided.

  蒂巴因和6-脱甲氧基蒂巴因的苄基化反应产生不同的产物混合物。对于观察到的5β-与7-苄基产物的比例差异和7-苄基产物的C环电子结构的偏差给出了解释。实现了吗啡喃-5,8-二烯，5,6-和6,7-二取代吗啡喃-6,8-二烯的酸催化重排，并提供了形成新的，可能具有多巴胺活性的紫杉醇的机理解释。