7α-(1-hydroxy-1-methylethyl)-6,7,8,14-tetrahydro-6,14-endo-ethenooripavine | 16530-46-4

• 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: 7α-(1-hydroxy-1-methylethyl)-6,7,8,14-tetrahydro-6,14-endo-ethenooripavine
• 英文别名: 4,5α-epoxy-19anti-(1-hydroxy-1-methyl-ethyl)-6-methoxy-17-methyl-6β,14-ethano-morphin-7-en-3-ol；(1R,2S,6R,14R,15R,19R)-19-(2-hydroxypropan-2-yl)-15-methoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,16-tetraen-11-ol
• CAS: 16530-46-4
• 化学式: C₂₃H₂₉NO₄
• 分子量: 383.488
• InChiKey: ZGKVSNGVCSJFTE-WEUAAKDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7α-(1-hydroxy-1-methylethyl)-6,7,8,14-tetrahydro-6,14-endo-ethenooripavine 在 盐酸 作用下， 生成 4,5α-epoxy-19anti-(1-hydroxy-1-methyl-ethyl)-17-methyl-6β,14-ethano-morphin-7-ene-3,6-diol
  参考文献：
  名称：

  吗啡-蒂巴因组的新型镇痛药和分子重排。第十六部分。6,14-内-etheno-7,8-dihydromorphine的某些衍生物

  摘要：

  通过乙酸中的溴化氢通过相应的可待因衍生物将6,14-内-乙基-四氢茶碱-7α-羧酸乙酯去甲基化为6,14-内-乙烯-7,8-二氢吗啡-7α-羧酸乙酯。6,14-内-Etheno -7,8-二氢7α（1-羟基-1-甲基乙基）可待因由碱以及由酸重新排列为一衍生物thebainone的。

  DOI：

  10.1039/j39690002569
• 作为产物：
  描述：

  蒂巴因 在 L-Selectride 作用下， 以 四氢呋喃 、 乙醚 、 甲苯 为溶剂， 反应 4.0h， 生成 7α-(1-hydroxy-1-methylethyl)-6,7,8,14-tetrahydro-6,14-endo-ethenooripavine
  参考文献：
  名称：

  L-Selectride as a General Reagent for the O-Demethylation and N-Decarbomethoxylation of Opium Alkaloids and Derivatives¹

  摘要：

  L-Selectride was shown to be an efficient and general O-demethylating agent for the opium alkaloids and their derivatives and also an efficient reagent for the cleavage of methyl carbamates, thus offering a convenient method for the N-demethylation of opioids. Further, it was shown that by choice of reaction conditions it is possible to achieve both N-decarbomethoxylation and O-demethylation in one pot, or only render N-decarbomethoxylation in high yield without accompanying O-demethylation.

  DOI：

  10.1021/jo9801972

文献信息

• Non-CNS Acting Opiates Bearing Guanidino Substituents
  作者：Kamani R. Subasinghe、W. Roy Jackson、Jacqui F. Young、Maria Papanastasiou、Bevyn Jarrott

  DOI：10.1071/ch03199

  日期：——

  A series of guanidino-substituted opiates based on morphine, diprenorphine, and buprenorphine have been synthesized. Guanidines with aryl and alkyl substituents as well as unsubstituted ones have been attached to the opiate nucleus with spacer units of varying length. The spacer groups have mainly been attached to the opiates via the opiate nitrogen atom. A few compounds involving attachment through opiate oxygen atoms have been prepared, but were found to be ineffective as analgesics.The activity of the compounds as analgesics has been evaluated using the phenylquinone (PQ) abdominal-constriction test and their ability to enter the CNS evaluated with the Straub tail response. The compounds most active in the PQ abdominal-constriction test and showing no Straub tail behaviour contained aryl-substituted guanidines.

  我们合成了一系列以吗啡、二丙诺啡和丁丙诺啡为基础的胍基取代鸦片制剂。带有芳基和烷基取代基以及未取代基的胍基通过不同长度的间隔单元连接到阿片剂的核上。间隔基主要通过阿片剂的氮原子连接到阿片剂上。利用苯醌（PQ）腹部收缩试验评估了这些化合物的镇痛活性，并利用斯特劳布尾反应评估了它们进入中枢神经系统的能力。在 PQ 腹部收缩试验中活性最强且没有 Straub 尾部反应的化合物含有芳基取代的鸟嘌呤。
• Novel analgesics and molecular rearrangements in the morphine-thebaine group. III. Alcohols of the 6,14-endo-ethenotetrahydrooripavine series and derived analogs of N-allylnormorphine and -norcodeine
  作者：Kenneth W. Bentley、Denis G. Hardy

  DOI：10.1021/ja00989a032

  日期：1967.6

  affected only the meth-oxy1 group attached to (2-3, that at C-6 remaining undisturbed. From the point of view of analgesic activity , however, the retention of the C-6 methoxyl group is advantageous, since methylation of the hy-droxyl group at this position in morphine and codeine enhances the activity. The demethylation of the C-3 methoxyl group in the codeine-thebaine group under alkaline conditions

  通式结构 IV 和 V 的仲醇和叔醇是通过本系列第 I1 部分中描述的相应碱 I 和 I1 的脱甲基化制备的。如此获得的酚类是具有极高效力的镇痛剂，其强度是吗啡的 12,000 倍，这是史无前例的。该系列和更早系列的碱已通过 N-氰基化合物和新的 N，N'-亚甲基双化合物 XI11 转化为通式结构 XI 和 XI1 的 N-烯丙基诺吗啡和 N-烯丙基诺可待因的类似物。 I和I1与偶氮二羧酸甲酯。XI1 系列的某些碱基是具有前所未有效力的吗啡拮抗剂，高达 N-烯丙基吗啡的 150 倍。在之前的论文中，报道了通式结构 I 和 I1 的两个系列 I 可待因衍生物的制备，其中许多成员作为镇痛剂的活性比以前在吗啡-蒂巴因组中制备的任何碱都要高得多。由于可待因衍生物去甲基化为相应的吗啡衍生物几乎总是导致镇痛活性显着增加，因此结构 I 和 I1 的大部分醇都转化为相关的酚类。由于醇非常容易进行酸催化重排
• Novel analgesics and molecular rearrangements in the morphine–thebaine group. Part XIV. Substitution in the aromatic nucleus in derivatives of 6,14-endo-ethenotetrahydrothebaine
  作者：K. W. Bentley、J. D. Bower、A. C. B. Smith

  DOI：10.1039/j39690002241

  日期：——

  The tetrahydrothebaine ester (1; R = H) has been acetylated with acetic acid and trifluoroacetic anhydride. The product (1; R = Ac) has been reduced to the secondary alcohol and converted by the Schmidt reaction into the acetyl derivative of the amine (1; R = NH2), which is the product of reduction of the 1-nitro-compound obtainable by nitration of the ester (1; R = H). Chlorination of the tetrahydrothebaine

  四氢茶碱酯（1； R = H）已用乙酸和三氟乙酸酐乙酰化。产物（1; R = Ac）已还原为仲醇，并通过Schmidt反应转化为胺（1; R = NH 2）的乙酰基衍生物，该胺是1-硝基-硝基的还原产物。可通过酯化硝化得到的化合物（1； R = H）。将四氢蒂巴因醇（2； R = Me）氯化，得到1-氯化合物，该化合物已脱甲基化为相关的苯酚。通过曼尼希反应，苯酚（2； R = H）已转化为2-氨基化合物。
• Synthesis and opioid activity of novel 6-substituted-6-demethoxy-ethenomorphinans
  作者：Barbara Czakó、János Marton、Sándor Berényi、Katarzyna Gach、Jakub Fichna、Martin Storr、Géza Tóth、Attila Sipos、Anna Janecka

  DOI：10.1016/j.bmc.2010.03.068

  日期：2010.5

  A set of novel 6-substituted orvinols was synthesized and pharmacologically characterized in order to explore the effect of the polarity and steric effects of these new moieties on the opioid activity. It was revealed that longer 6-O-alkyl chains led to increased agonistic activities, while the lack of C6-etheral oxygen gave rise to an antagonistic profile at the opioid receptors in the mouse ileum. (C) 2010 Elsevier Ltd. All rights reserved.
• Novel analgetics and molecular rearrangements in the morphine-thebaine group. XVIII. 3-Deoxy-6,14-endo-etheno-6,7,8,14-tetrahydrooripavines
  作者：John William Lewis、Michael J. Readhead

  DOI：10.1021/jm00297a041

  日期：1970.5