(-)-4-hydroxy-17-methylmorphinan-6-one | 74207-10-6

• 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-hydroxy-17-methylmorphinan-6-one
• 英文别名: (-)-4-hydroxy-N-methylmorphinan-6-one；4-hydroxy-17-methylmorphinan-6-one；4-hydroxy-N-methylmorphinan-6-one；(-)-4-hydroxy-6-keto-N-methylmorphinan；(+)-4-Hydroxy-N-methylmorphinan-6-one；(1S,9R,10R)-3-hydroxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
• CAS: 74207-10-6
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: QYNINOVRFBUMAB-VBQJREDUSA-N

物化性质

• 沸点：
  444.0±45.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-4-hydroxy-17-methylmorphinan-6-one 在 palladium on activated charcoal ammonium chloride 、 氢气 、 溴 、 sodium acetate 、 potassium hydrogencarbonate 、 锌 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 97.33h， 生成 (-)-4-hydroxy-N-formylmorphinan-6-one
  参考文献：
  名称：

  (−)-4-Hydroxy-N-formylmorphinan-6-one, a versatile intermediate for the synthesis of 3-deoxyopioids

  摘要：

  (-)-4-羟基-N-甲酰吗啡酮-6-酮（4）从酮1通过碳酸酯2和酮3的N-甲酰化反应，总产率为70%制备而成。4的溴化反应产物可以得到6-酮吗啡酮7或酮8，具体取决于所采用的反应条件。两种溴化酮7和8均可通过标准反应转化为4,5-环氧-N-甲基吗啡酮-6-酮（1）。这些研究表明，酮吗啡酮4是一种多功能中间体，非常适合用于合成4-羟基吗啡酮和3-去氧阿片类药物。

  DOI：

  10.1139/v80-292
• 作为产物：
  描述：

  盐酸纳曲酮 在 吡啶 、 盐酸 、 platinum(IV) oxide 、 lithium aluminium tetrahydride 、 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 1,1,2,2-四氯乙烷 为溶剂， 反应 103.0h， 生成 (-)-4-hydroxy-17-methylmorphinan-6-one
  参考文献：
  名称：

  Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists

  摘要：

  The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the delta opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the 8 receptor over the mu receptor than the corresponding SN-28 derivatives with the 3-hydroxy group (SN-11, 23, 28). Derivatives with the 4-hydroxy group showed potent agonist activities for the 5 receptor in the [S-35]GTPyS binding assay. Although the 17-cyclopropylmethyl derivative (SN-11) with a 3-hydroxy group showed the lowest selectivity for the delta receptor among the morphinan derivatives, the agonist activity toward the delta receptor was the most potent for candidates with the 3-hydroxy group. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.047

文献信息

• Structure-Activity Relationships of Oxygenated Morphinans. I. 4-Mono- and 3,4-dimethoxy-N-methylmorphinans and -N-methyl-morphinan-6-ones with unusually high antinociceptive potency. Preliminary communication
  作者：Arthur E. Jacobson、Fu-Lian Hsu、Maria D. Rozwadowska、Helmut Schmidhammer、Louise Atwell、Arnold Brossi、Fedor Medzihradsky

  DOI：10.1002/hlca.19810640506

  日期：1981.7.22

  The antinociceptive potency and receptor affinity of several optically active aromatic mono- and di-oxygenated N-methylmorphinans and N-methylmorphinan-6-ones, prepared from natural morphine, were determined. Thus, in order of antinociceptive potency, 4-methoxy-N-methylmorphinan-6-one ≈ 3,4-dimethoxy-N-methylmorphinan-6-one ≈ 3,4-dimethoxy-N-methylmorphinan > 4-methoxy-N-methylmorphinan ≈ 4-acetox

  测定了由天然吗啡制得的几种光学活性芳族单加氧和双加氧的N-甲基吗啡喃和N-甲基吗啡喃-6-的抗伤害力和受体亲和力。因此，在镇痛效力的次序，4-甲氧基Ñ -methylmorphinan -6-酮≈3,4-二甲Ñ -methylmorphinan -6-酮≈3,4-二甲Ñ -methylmorphinan> 4-甲氧基- ñ -甲基吗啡喃≈4-乙酰氧基-N-甲基吗啡喃-6->> 4-乙酰氧基-N-甲基吗啡喃≈4-羟基-N-甲基吗啡喃-6-一个≈4-羟基-N-甲基吗啡喃。4-羟基化合物的效力比吗啡稍弱，发现4-甲氧基和3,4-二甲氧基化合物的效力是吗啡的三倍。4-甲氧基-N-甲基吗啡喃-6-的阿片受体亲和力为吗啡的三分之一；这对非酚类化合物具有极高的亲和力。
• Structure Determination of Brominated Morphinan-6-ones by13C-NMR. Spectroscopy: A novel closure of the oxygen bridge using 4-acetoxymorphinan-6-ones
  作者：Arnold Brossi、Fu-Lian Hsu、Kenner C. Rice、Maria D. Rozwadowska、Helmut Schmidhammer、Charles D. Hufford、Chian Chian Chiang、Isabella L. Karle

  DOI：10.1002/hlca.19810640545

  日期：1981.7.22

  Bromination of (−)-4-hydroxy-N-methylmorphinan-6-one (3), prepared from natural morphine, with 1 mol of bromine in acetic acid, afforded the 1-bromo ketone 5. The structure of 5 was assigned by 13C-NMR.spectroscopy, and confirmed by X-ray diffraction analysis of its hydrobromide salt. It is suggested that monobromination of synthetic (±)-2,4-dihydroxy-N-formylmorphinan-6-one (7) takes in principle

  由天然吗啡制备的（-）-4-羟基-N-甲基吗啡喃6-1（3）与1摩尔的溴在乙酸中的溴化，得到1-溴代酮5。5的结构通过13 C-NMR光谱确定，并通过其氢溴酸盐的X射线衍射分析确认。建议合成（±）-2,4-二羟基-N-甲酰基吗啡喃-6-一（7）的单溴化原理相似，尽管一级反应产物9的13 C-NMR谱不能由于在常用溶剂中不溶而被测量。（-）-4-乙酰氧基-N的单溴化天然系列的-甲酰基吗啡喃-6-（12）和合成系列的（±）-2,4-二乙酰氧基-N-甲酰基吗啡喃-6-one（8），然后用钾处理单溴代酮在甲醇中的碳酸根导致O-桥的闭合，并且在酸水解后分别提供相应的4,5-环氧-吗啡喃-6-（-）- 16和（±）-17。闭环反应的这种变化代表了一种新颖且方便的方法，该方法将4-羟基吗啡喃-6-酮转化为其相应的4,5-环氧吗啡喃-6-酮，而无需涉及芳族溴化且仅含1摩尔溴。
• 6-Keto-morphinan analgesics
  申请人：The United States of America as represented by Secretary of the

  公开号：US04388463A1

  公开（公告）日：1983-06-14

  This patent application describes the preparation and properties of novel and highly potent morphinan analgesics. The compounds include narcotic agnoists as well as narcotic antagonists and are represented by the following formula: ##STR1## R.sub.1 =OCH.sub.3, OCOCH.sub.3, H R.sub.2 =CH.sub.3, CH.sub.2 --CH.dbd.CH.sub.2, ##STR2## CH.sub.2 CH.sub.2 C.sub.6 H.sub.5

  这项专利申请描述了新型和高效的吗啡类镇痛剂的制备和性质。这些化合物包括麻醉药激动剂和麻醉药拮抗剂，并由以下公式代表：##STR1## R.sub.1 =OCH.sub.3, OCOCH.sub.3, H R.sub.2 =CH.sub.3, CH.sub.2 --CH.dbd.CH.sub.2, ##STR2## CH.sub.2 CH.sub.2 C.sub.6 H.sub.5
• Antitussive 6-keto morphinans of the (+)-series
  申请人：The United States of America as represented by the Department of Health

  公开号：US04552962A1

  公开（公告）日：1985-11-12

  The present invention is concerned with dextrorotatory morphinans, which are illustrated by (+)-4-methoxy-6-keto-N-methylmorphinan. Related compounds which also have been introduced as cough-suppressing agents include the (+)-3-methoxy-N-methylmorphinans (ROMILAR-Roche).

  本发明涉及右旋型吗啡类化合物，其中包括(+)-4-甲氧基-6-酮-N-甲基吗啡烷。相关的化合物也已被引入作为止咳剂，其中包括(+)-3-甲氧基-N-甲基吗啡烷（ROMILAR-Roche）。
• (-)-4-Hydroxymorphinanones: their synthesis and analgesic activity
  作者：Awinash Manmade、Haldean C. Dalzell、John F. Howes、Raj K. Razdan

  DOI：10.1021/jm00144a013

  日期：1981.12

  A facile procedure is described for the conversion of morphine, via the diphosphate ester derivative 1 followed by catalytic reduction and treatment with Li/NH3, to 3-deoxy-7,8-dihydromorphine (3). Oxidation with benzophenone tert-butoxide converted 3 to the ketone 4, which on treatment with Zn/NH4Cl formed (-)-4-hydroxymorphinan-6-one 5. Reaction of 5 with diazomethane formed the methyl ether 6. The N-cyclopropylmethyl analogues of 4 and 5 were also prepared, i.e., 8c and 9 from 4. The antinociceptive activity of these compounds was tested. Compounds 5, 6, 8c, and 9 showed potent antiwrithing activity and, based on these data, a structure-activity relationship in morphinans is discussed.