(-)-4,5-epoxymorphinan-6-one | 31769-01-4

• 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: (-)-4,5-epoxymorphinan-6-one
• 英文别名: 4,5-epoxymorphinan-6-one；(4R,4aR,7aR,12bS)-2,3,4,4a,5,6,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 31769-01-4
• 化学式: C₁₆H₁₇NO₂
• 分子量: 255.316
• InChiKey: UQENVGBKYDWGGR-OJXGSEEGSA-N

物化性质

• 沸点：
  448.3±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-4,5-epoxymorphinan-6-one 在 potassium carbonate 、 氯化铵 、 锌 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 30.0h， 生成 酮啡诺
  参考文献：
  名称：

  (-)-4-Hydroxymorphinanones: their synthesis and analgesic activity

  摘要：

  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.

  DOI：

  10.1021/jm00144a013
• 作为产物：
  描述：

  4,5-epoxy-N-(2,2,2-trichloroethoxycarbonyl)morphinan-6-one 在 锌 作用下， 以 溶剂黄146 为溶剂， 以87%的产率得到(-)-4,5-epoxymorphinan-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

文献信息

• [EN] A METHOD OF PREPARATION OF 4,5alpha-EPOXY-6-OXOMORPHINAN DERIVATIVES<br/>[FR] METHODE DE PREPARATION DE DERIVES DE 4,5 DOLLAR G(A)-EPOXY-6-OXOMORPHINANE
  申请人：ZENTIVA AS

  公开号：WO2005100361A1

  公开（公告）日：2005-10-27

  A method of preparation of 4,5α-epoxy-6-oxomorphinan derivatives of formula (I), wherein R1 is hydrogen, methyl, or ethyl and R2 is hydrogen, methyl, cyclobutylmethyl or benzyl, in which compounds of formula (II), wherein R1 and R2 are as defined with respect to compounds (I), are isomerized into compounds of formula (I) in the presence of a mixed catalyst containing at least two elements from the group of platinum metals. The method provides the product in high yield and with low contents of impurities.

  一种制备4,5α-环氧-6-酮吗啡衍生物的方法，其中R1为氢、甲基或乙基，R2为氢、甲基、环丁基甲基或苄基，在该方法中，式（II）化合物，在其中R1和R2如与化合物（I）相对应定义，存在于含有铂族金属至少两种元素的混合催化剂的情况下，异构化为式（I）化合物。该方法以��产率和低杂质含量提供产品。
• 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。
• 7,7-Ditosyloxymethyl-4,5 alpha-epoxy-morphinan-6-ols and their use as intermediates in the production of epoxymorphinan derivatives
  申请人：MILES LABORATORIES, INC.

  公开号：EP0039444A1

  公开（公告）日：1981-11-11

  Disclosedare7,7-ditosyloxymethyl-4,5α-epoxymorphi- nan-6-ol compounds characterized by the formula: wherein R is H, CH3 or CH2CH3. These compounds are useful as intermediates in the production of a series of epoxy-morphinan derivatives.

  本发明公开了7,7-二丁氧基甲基-4,5α-环氧吗啉-6-醇化合物，其特征在于该化合物具有如下式： 其中 R 是 H、CH3 或 CH2 。这些化合物可用作生产一系列环氧吗啡烷衍生物的中间体。
• 7- and 7,8-substituted 4,5-alpha-epoxymorphinan-6-ones and therapeutically active compositions containing them
  申请人：MILES LABORATORIES, INC.

  公开号：EP0023576B1

  公开（公告）日：1982-06-23
• US4272541A
  申请人：——

  公开号：US4272541A

  公开（公告）日：1981-06-09