(5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxaldehyde | 16193-25-2

• 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: (5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxaldehyde
• 英文别名: thevinal；4,5α-epoxy-3,6-dimethoxy-17-methyl-6α,14α-etheno-morphinane-7α-carbaldehyde；4,5α-Epoxy-3,6-dimethoxy-17-methyl-6α,14α-aetheno-morphinan-7α-carbaldehyd；(1R,2S,6R,14R,15R,16S)-11,15-dimethoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,18-tetraene-16-carbaldehyde
• CAS: 16193-25-2
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: GPLOEQSNMDQKMY-GEAUKGQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.59
• 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：

  (5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxaldehyde 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 甲苯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 25.0h， 生成 (αR,5α,6α,7α,14α)-4,5-epoxy-18,19-dihydro-3,6-dimethoxy-17-methyl-α-phenyl-6,14-ethenomorphinan-7-methanol
  参考文献：
  名称：

  Thevinols的甲酸催化重排（= 4,5-环氧-3,6-二甲氧基- α，17二甲基-6,14- ethenomorphinan -7-基甲醇）及其类似物插烯：5影响β -甲基换人

  摘要：

  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。

  DOI：

  10.1002/hlca.200390185
• 作为产物：
  描述：

  蒂巴因 、 丙烯醛 以 苯 为溶剂， 反应 16.0h， 以100%的产率得到(5α,6α,7α,14α)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxaldehyde
  参考文献：
  名称：

  Thevinols的甲酸催化重排（= 4,5-环氧-3,6-二甲氧基- α，17二甲基-6,14- ethenomorphinan -7-基甲醇）及其类似物插烯：5影响β -甲基换人

  摘要：

  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。

  DOI：

  10.1002/hlca.200390185

文献信息

• Synthesis of New Nepenthone Derivatives
  作者：János Marton、Zoltán Szabó、Csaba Simon、Sándor Hosztafi、Sándor Makleit

  DOI：10.1002/jlac.199619961025

  日期：1996.10

  Hydrogenation of nepenthone (3a) leads to a mixture of dihydronepenthone (3c) and the secondary alcohol (20S)-4b. The enantiomeric secondary alcohol (20S)-4b is prepared from the 7α-formyl-6,14-ethenomorphinan derivative 3b by reaction with phenylmagnesium bromide to afford a mixture of the diastereoisomeric alcohols 4a. Hydrogenation of 4a leads to (20S)-4b and (20R)-4b, which are separated by fractional

  萘甲酮（3a）的氢化产生了二氢苯酮（3c）和仲醇（20 S）-4b的混合物。对映体仲醇（20 S）-4b由7α-甲酰基-6,14-乙炔吗啡喃衍生物3b与苯基溴化镁反应制得，得到非对映异构醇4a的混合物。4a的氢化导致（20 S）-4b和（20 R）-4b，它们通过分步结晶分离。（20 S）-4b的构象和（20 R）-4b通过NOE差异实验确定。
• Control of the diastereoselectivity at C(20) in the formation of C(21)-fluorinated thevinols
  作者：Irina V. Sandulenko、Ekaterina S. Kovaleva、Maria V. Zelentsova、Asmik A. Ambartsumyan、Sergey N. Gorlov、Anastasia A. Danshina、Rinat R. Aysin、Sergey K. Moiseev

  DOI：10.1039/d2ob02144g

  日期：——

  C(20)-alcohols 12 can be prepared either by reaction of 21,21,21-trifluorothevinone (9) with RM (R = alkyl; M = Li, MgX) or by reaction of thevinone (2) and related non-fluorinated ketones with CF3SiMe3. In general, alcohols 12 were formed as mixtures of the C(20)-epimers, with the major epimers of the alcohols obtained from the aforementioned reactions exploiting RLi vs. CF3SiMe3 with opposite absolute

  据报道，在 20- R -21,21,21-三氟茶乙烯醇 ( 12 ) 的合成中，有一种方法可以控制 C(20) 的立体选择性，阿片类药物配体在与 C(20) 周围环境相关的药效团中掺入了氟原子) 碳原子。C(20)-醇12可通过 21,21,21-三氟茶乙烯酮 ( 9 ) 与 RM（R = 烷基；M = Li、MgX）反应或通过茶乙烯酮 ( 2 ) 与相关非-氟化酮与 CF 3 SiMe 3。通常，醇12形成为 C(20)-差向异构体的混合物，其中醇的主要差向异构体是从上述利用 RLi 的反应中获得的与在 C(20) 处具有相反绝对构型的CF 3 SiMe 3相比。氟化醇12的一些单独的 C(20)-差向异构体通过普通结晶以纯形式从反应混合物中分离出来。酮与 RMgX（R ≠ Me）和 RLi（R = 叔或仲烷基）的反应导致羰基功能减少，生成仲醇11a、b而不是叔醇12。发现盐的添加剂会
• Buprenorphine analogs
  申请人：Purdue Pharma L.P.

  公开号：EP2703404A1

  公开（公告）日：2014-03-05

  The present invention is directed to Buprenorphine Analog compounds of the Formula I, Formula II or Formula III shown below, wherein R1, R2, R8, R3, R3a, R3b, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain and other conditions modulated by activity of opioid and ORL1 receptors.

  本发明涉及下式 I、式 II 或式 III 所示的丁丙诺啡类似物化合物，其中 R1、R2、R8、R3、R3a、R3b、X、Z 和 Y 如本文所定义。 本发明的化合物可用于治疗疼痛和其他受阿片类和 ORL1 受体活性调节的病症。
• Cinnamoyl Derivatives of 7α-Aminomethyl-6,14-<i>endo</i>-ethanotetrahydrothebaine and 7α-Aminomethyl-6,14-<i>endo</i>-ethanotetrahydrooripavine and Related Opioid Ligands
  作者：David Rennison、Adrian P. Neal、Gerta Cami-Kobeci、Mario D. Aceto、Fernando Martinez-Bermejo、John W. Lewis、Stephen M. Husbands

  DOI：10.1021/jm070255o

  日期：2007.10.1

  A new series of ligands has been synthesized where the cinnamoyl group of the 14-cinnamoylamino morphinones has been introduced to the 7 alpha-substituent of the 6,14-bridged oripavine series. In vitro the compounds were mostly low efficacy partial agonists or antagonists with some selectivity for the mu opioid receptor, with evidence of mu efficacy in vivo. The similarity in SAR between these 6,14-bridged oripavines and the 14-cinnamoylamino series suggests a similar mode of interaction with the mu. opioid receptor.
• 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.