(-)-4,5α-epoxy-3,6-dimethoxy-17-methyl-7-propylidene-6α,14α-ethenoisomorphinan | 145986-51-2

• 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-17-methyl-7-propylidene-6α,14α-ethenoisomorphinan
• 英文别名: 7-ethylidenetetrahydro-6,14-endo-ethenothebaine；4,5α-epoxy-19-(E)-ethylidene-3,6-dimethoxy-17-methyl-6β,14-ethano-morphin-7-ene；(1R,2S,6R,14R,15R,19E)-19-ethylidene-11,15-dimethoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,16-tetraene
• CAS: 145986-51-2
• 化学式: C₂₃H₂₇NO₃
• 分子量: 365.472
• InChiKey: ZAUKRWOEVKVMAE-YGQQGQJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-4,5α-epoxy-3,6-dimethoxy-17-methyl-7-propylidene-6α,14α-ethenoisomorphinan 在 palladium on activated charcoal 氢气 作用下， 以 溶剂黄146 为溶剂， 生成 4,5α-epoxy-7-(E)-ethylidene-3,6-dimethoxy-17-methyl-6α,14α-ethano-morphinane
  参考文献：
  名称：

  吗啡-蒂巴因组的新型镇痛药和分子重排。第二十七部分。7-亚烷基和7α-乙烯基-6,14-内-乙炔-6,7,8,14-四氢噻吩

  摘要：

  在非对映异构6,14- C-19仲甲苯磺酸酯的脱甲苯磺酰化内切-ethenotetrahydrothebaine系列进行了研究。通过浓盐酸将产物7-亚烷基-和7α-乙烯基-6,14-内-乙烯基-6,7,8,14-四氢噻吩重新排列成桥联的蒂巴酮。

  DOI：

  10.1039/p19720000881
• 作为产物：
  描述：

  (R)-1-((4R,4aR,7R,7aR,12bS,14R)-7,9-dimethoxy-3-methyl-1,2,3,4,7,7a-hexahydro-7,4a-ethano-4,12-methanobenzofuro[3,2-e]isoquinolin-14-yl)ethan-1-ol 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 (-)-4,5α-epoxy-3,6-dimethoxy-17-methyl-7-propylidene-6α,14α-ethenoisomorphinan
  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

文献信息

• 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.
• Novel analgesics and molecular rearrangements in the morphine–thebaine group. Part XXVII. 7-Alkylidene- and 7α-vinyl-6,14-endo-etheno-6,7,8,14-tetrahydrothebaines
  作者：J. W. Lewis、M. J. Readhead

  DOI：10.1039/p19720000881

  日期：——

  diastereoisomeric C-19 secondary tosylates in the 6,14-endo-ethenotetrahydrothebaine series has been investigated. The products, 7-alkylidene- and 7α-vinyl-6,14-endo-etheno-6,7,8,14-tetrahydrothebaines, are rearranged by concentrated hydrochloric acid to bridged thebainones.

  在非对映异构6,14- C-19仲甲苯磺酸酯的脱甲苯磺酰化内切-ethenotetrahydrothebaine系列进行了研究。通过浓盐酸将产物7-亚烷基-和7α-乙烯基-6,14-内-乙烯基-6,7,8,14-四氢噻吩重新排列成桥联的蒂巴酮。