(-)-4,5α-epoxy-3,6-dimethoxy-5,N-dimethyl-6α,14α-ethenoisomorphinan-7α-methanol | 129052-42-2

• 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: (-)-4,5α-epoxy-3,6-dimethoxy-5,N-dimethyl-6α,14α-ethenoisomorphinan-7α-methanol
• 英文别名: 5β,20-dimethylthevinol
• CAS: 129052-42-2
• 化学式: C₂₅H₃₃NO₄
• 分子量: 411.541
• InChiKey: YXOXUJMHKADYOS-DKABMLEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.08
• 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：
  0.68
• 拓扑面积：
  51.16
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (-)-4,5α-epoxy-3,6-dimethoxy-5,N-dimethyl-6α,14α-ethenoisomorphinan-7α-methanol 在 氢氧化钾 作用下， 以 水 、 乙二醇 为溶剂， 反应 6.0h， 以68%的产率得到(-)-4,5α-epoxy-3-hydroxy-6-methoxy-5,N-dimethyl-6α,14α-ethenoisomorphinan-7α-methanol
  参考文献：
  名称：

  Woudenberg, R. H.; Lie, T. S.; Maat, L., Recueil des Travaux Chimiques des Pays-Bas, 1990, vol. 109, p. 353 - 357

  摘要：

  DOI：
• 作为产物：
  描述：

  5β-methylthebaine 在 magnesium 作用下， 反应 96.0h， 生成 (-)-4,5α-epoxy-3,6-dimethoxy-5,N-dimethyl-6α,14α-ethenoisomorphinan-7α-methanol
  参考文献：
  名称：

  Woudenberg, R. H.; Lie, T. S.; Maat, L., Recueil des Travaux Chimiques des Pays-Bas, 1990, vol. 109, p. 353 - 357

  摘要：

  DOI：

文献信息

• Formic Acid Catalyzed Rearrangement of Thevinols (=4,5-Epoxy-3,6-dimethoxy-α,17-dimethyl-6,14-ethenomorphinan-7-methanols) and Their Vinylogous Analogues: Effects of 5β-Methyl Substitution
  作者：Peter Grundt、Fernando Martinez-Bermejo、John W. Lewis、Stephen M. Husbands

  DOI：10.1002/hlca.200390185

  日期：2003.7

  equivalent 14-alkenyl-7,8-dihydrocodeinones undergo further rearrangement (Scheme 1 and Table). Introduction of a 5β-methyl group allows the 18,19-dihydrothevinol precursors to be rearranged to 14-alkenyl-7,8-dihydrocodeinones, but similar manipulation of the vinylogues of these thevinols is generally unable to prevent full rearrangement to 5,14-bridged thebainone derivatives.

  在少数情况下，可以通过对乙烯醇进行甲酸处理来获得14个烯基可待因酮（= 14-烯基-7,8-二氢-4,5-环氧-3-甲氧基-17-甲基吗啡喃-6-酮）（ ＝ 4，5-环氧-3，6-二甲氧基-α，17-二甲基-6，14-乙炔吗啡喃-7-甲醇），但是在这些条件下，等效的14-烯基-7，8-二氢可待因酮经历进一步的重排（方案1和表）。5介绍β -甲基组允许18,19 dihydrothevinol前体将被重新排列到14链烯基-7,8- dihydrocodeinones，但这些thevinols的vinylogues的类似操作一般不能充分防止重排至5,14桥联的蒂巴因酮衍生物。
• 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
  作者：Leendert Maat、Richard H. Woudenberg、Gerrit J. Meuzelaar、Joannes T.M. Linders

  DOI：10.1016/s0968-0896(98)00267-3

  日期：1999.3

  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.