1-[(5α,7α)-4,5-epoxy-3-hydroxy-6-methoxy-17-methyl-6,14-ethenomorphinan-7-yl]ethanone | 22329-04-0

• 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: 1-[(5α,7α)-4,5-epoxy-3-hydroxy-6-methoxy-17-methyl-6,14-ethenomorphinan-7-yl]ethanone
• 英文别名: 1-(4,5α-epoxy-3-hydroxy-6-methoxy-17-methyl-6α,14α-etheno-morphinan-7α-yl)-ethanone；1-[(1R,2S,6R,14R,15R,16S)-11-hydroxy-15-methoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,18-tetraen-16-yl]ethanone
• CAS: 22329-04-0
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: PAQRTKYVYYRTCM-GEAUKGQYSA-N

物化性质

• 沸点：
  529.0±50.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[(5α,7α)-4,5-epoxy-3-hydroxy-6-methoxy-17-methyl-6,14-ethenomorphinan-7-yl]ethanone 在 palladium 10% on activated carbon 、 氢气 、 酒石酸 、 三乙胺 作用下， 以 水 、 甲苯 为溶剂， 40.0~80.0 ℃ 、101.33 kPa 条件下， 反应 16.5h， 生成 Ethanone, 1-[(5alpha,7alpha)-3-[(ethoxycarbonyl)oxy]-4,5-epoxy-18,19-dihydro-6-methoxy-17-methyl-6,14-ethenomorphinan-7-yl]-
  参考文献：
  名称：

  通过钯催化的N-去甲基化/酰化和/或伴随的O-去甲基化，从蒂巴因和/或奥利巴韦改进丁丙诺啡的合成

  摘要：

  据报道，通过钯催化的N-去甲基化/酰化可以改善丁丙诺啡的制备方法。研究了三种途径，并比较了总产量。首先涉及从蒂巴因获得的高级中间体的N-去甲基化/酰化，然后将N-乙酰胺水解并用环丙基甲基溴烷基化和/或还原N用Schwartz试剂形成一个-乙酰基，然后进行N-烷基化。第二种方法是在N-去甲基化/酰化方案中使用环丙基羧酸酐，然后通过氢化铝锂或在氢化硅烷化条件下还原环丙基羧酰胺。这两个途径均起源于蒂巴因，因此需要将O-去甲基化作为最后一步。第三种途径采用的是N-去甲基化/酰化序列，其起始位置为牛至而不是蒂巴因，从而避免了O-去甲基化。比较了这些路线的总体效率，并提供了所有新化合物的实验数据和光谱数据。

  DOI：

  10.1002/adsc.201100807
• 作为产物：
  描述：

  蒂巴因 在 L-Selectride 作用下， 以 甲苯 为溶剂， 反应 2.5h， 生成 1-[(5α,7α)-4,5-epoxy-3-hydroxy-6-methoxy-17-methyl-6,14-ethenomorphinan-7-yl]ethanone
  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

• Novel analgesics and molecular rearrangements in the morphine–thebaine group. Part VIII. 7-Alkyl-6,14-endo-ethenotetrahydrothebaine and related compounds
  作者：K. W. Bentley、D. G. Hardy、J. W. Lewis、M. J. Readhead、W. I. Rushworth

  DOI：10.1039/j39690000826

  日期：——

  The preparation of 7-alkyl derivatives of 6,14-endo-ethenotetrahydrothebaine and 6,14-endo-ethenotetrahydro-oripavine, including N-alkyl, N-alkenyl, and N-cyclopropylmethyl analogues, is described.

  描述了6，14-内-乙炔四氢蒂巴因和6，14-内-乙炔四氢-奥巴韦的7-烷基衍生物的制备，包括N-烷基，N-烯基和N-环丙基甲基类似物。
• [EN] PROCESS FOR PREPARING 7&bgr;-SUBSTITUTED 6α,14α -ETHENOMORPHINANS AND 7&bgr;-SUBSTITUTED 6α,14α-ETHANOMORPHINANS<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'ÉTHÉNO-6&Agr;,14&Agr;-MORPHINANES À SUBSTITUTION 7&Bgr; ET D'ÉTHANO-6&Agr;,14&Agr;-MORPHINANES À SUBSTITUTION 7&Bgr;
  申请人：RHODES TECHNOLOGIES

  公开号：WO2014102591A1

  公开（公告）日：2014-07-03

  The application is directed to a process for increasing the proportion of 7β-epimer in an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α,14α-ethanomorphinan, and specifically of compounds of Formula (I), wherein G, R2-R4, and are defined as set forth in the specification. The application is also directed to a process for purifying the 7β-epimer from an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α, 14α-ethanomorphinan. The application is also directed to a process for preparing 7β-substituted compounds of Formula Vb wherein G and R2 -R5 are defined as set forth in the specification.

  该申请涉及一种用于增加7-取代6α,14α-乙烯基吗啡或7-取代6α,14α-乙烷基吗啡的7α/7β-异构体混合物中7β-异构体比例的方法，具体地，涉及到公式（I）中G、R2-R4的化合物的方法，其中G、R2-R4的定义如规范中所述。该申请还涉及从7-取代6α,14α-乙烯基吗啡或7-取代6α,14α-乙烷基吗啡的7α/7β-异构体混合物中纯化7β-异构体的方法。该申请还涉及制备公式Vb中G和R2-R5定义如规范中所述的7β-取代化合物的方法。
• Etorphine-Related Ferrocenyl-Substituted Morphinan Alkaloids
  作者：Gerhard Laus、Johannes Schütz、Herwig Schottenberger、Max Andre、Klaus Wurst、Mariana Spetea、Karl-Hans Ongania、Adrian G. Müller、Helmut Schmidhammer

  DOI：10.1002/hlca.200390268

  日期：2003.10

  The two diastereoisomeric ferrocenyl-substituted orvinols 2 and 3 were prepared. The modified alkaloids are still able to interact with opioid receptors (see Table). The ferrocene moiety allows highly selective and sensitive electrochemical detection. The X-ray crystal structure of the major isomer 2 was determined. The combination of a metallocene and a morphinan alkaloid holds promise for useful antitumor

  制备了两个非对映异构的二茂铁基取代的烯醇2和3。修饰的生物碱仍然能够与阿片样物质受体相互作用（见表）。二茂铁部分允许高度选择性和灵敏的电化学检测。确定了主要异构体2的X射线晶体结构。金属茂和吗啡喃生物碱的组合具有有用的抗肿瘤活性的希望。
• PROCESS FOR PREPARING 7BETA-SUBSTITUTED 6ALPHA,14ALPHA-ETHENOMORPHINANS AND 7BETA-SUBSTITUTED 6ALPHA,14ALPHA-ETHANOMORPHINANS
  申请人：REISCH Helge Alfred

  公开号：US20160068538A1

  公开（公告）日：2016-03-10

  The application is directed to a process for increasing the proportion of 7β-epimer in an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α,14α-ethanomorphinan, and specifically of compounds of Formula (I), wherein G, R 2 -R 4 , and are defined as set forth in the specification. The application is also directed to a process for purifying the 7β-epimer from an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α,14α-ethanomorphinan. The application is also directed to a process for preparing 7β-substituted compounds of Formula V b wherein G and R 2 -R 5 are defined as set forth in the specification.

  本申请涉及一种用于增加7-取代-6α,14α-乙烯吗啡烷或7-取代-6α,14α-乙烷吗啡烷的7α/7β-表异构体混合物中7β-表异构体比例的方法，具体地，涉及公式（I）中G，R2-R4的化合物。本申请还涉及一种从7-取代-6α,14α-乙烯吗啡烷或7-取代-6α,14α-乙烷吗啡烷的7α/7β-表异构体混合物中纯化7β-表异构体的方法。本申请还涉及一种制备公式Vb中G和R2-R5所定义的7β-取代化合物的方法。
• PROCESS FOR PREPARING OXYMORPHONE, NALTREXONE, AND BUPRENORPHINE
  申请人：HUANG Bao-Shan

  公开号：US20120196888A1

  公开（公告）日：2012-08-02

  Methods are provided which include converting oripavine to other opiates, including converting oripavine to naltrexone, buprenorphine, 14-hydroxymorphinone and/or converting 14-hydroxymorphinone to oxymorphone. Purification and salt formation are optionally included.

  本文提供了一种方法，其中包括将欧洲胡桃夹转化为其他鸦片类药物，包括将欧洲胡桃夹转化为纳曲酮、布洛芬、14-羟基吗啡酮和/或将14-羟基吗啡酮转化为氧吗啡酮。纯化和盐形成是可选的。