1-[(5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-yl]ethanone | 129052-40-0

• 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: 1-[(5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-yl]ethanone
• 英文别名: (-)-7α-acetyl-4,5α-epoxy-3,6-dimethoxy-5β,17-dimethyl-6α,14α-ethenoisomorphinan；(-)-7α-acetyl-4,5α-epoxy-3,6-dimethoxy-5,N-dimethyl-6α,14α-ethenoisomorphinan；1-[(1R,2S,6R,14R,15R,16S)-11,15-dimethoxy-5,14-dimethyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,18-tetraen-16-yl]ethanone
• CAS: 129052-40-0
• 化学式: C₂₄H₂₉NO₄
• 分子量: 395.499
• InChiKey: FNIFBBNFYMIPEZ-RXCHFPMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[(5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-yl]ethanone 在 氢氧化钾 作用下， 以 四氢呋喃 、 乙醚 、 水 、 乙二醇 为溶剂， 反应 8.0h， 生成 (-)-4,5α-epoxy-7α-<(R)-1-hydroxy-1-methylbutyl>-6-methoxy-5β,17-dimethyl-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：

  5β-methylthebaine 、 丁烯酮 反应 48.0h， 以100%的产率得到1-[(5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-yl]ethanone
  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。