N-cyclopropylmethylnororipavine | 14728-69-9

• 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: N-cyclopropylmethylnororipavine
• 英文别名: (4R,7aR,12bS)-3-(cyclopropylmethyl)-7-methoxy-2,3,4,7a-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-ol；(4R,7aR,12bS)-3-(cyclopropylmethyl)-7-methoxy-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-ol
• CAS: 14728-69-9
• 化学式: C₂₁H₂₃NO₃
• 分子量: 337.419
• InChiKey: YLKLDIVHRLJXGR-NQERJWCQSA-N

物化性质

• 熔点：
  163-164 °C
• 沸点：
  523.4±50.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-cyclopropylmethylnororipavine 在 过氧乙酸 、 palladium on activated charcoal 、 氢气 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 作用下， 以 水 、 丙酮 为溶剂， 5.0~20.0 ℃ 、345.01 kPa 条件下， 反应 15.75h， 生成 (R)-methylnaltrexone bromide
  参考文献：
  名称：

  Synthesis of Naltrexone and (R)-Methylnaltrexone from Oripavine via Direct Oxidation of Its Quaternary Salts

  摘要：

  (R)-Methylnaltrexone and naltrexone were each prepared in four steps from oripavine in practical yields. The procedure involved quaternization of oripavine with cyclopropylmethyl halides, singlet oxygen oxidation of the quaternary salts, and the reduction of endo peroxides to 14-hydroxyketone functionalities. (R)-Methylnaltrexone was prepared from the corresponding R-diastereomer of the oripavine salt. All diastereomeric mixtures of the quaternary salts were subjected to N-demethylation with sodium thiolate to yield cyclopropyl methylnororipavine, which was converted into naltrexone by peracid oxidation and hydrogenation according to established procedures.

  DOI：

  10.1055/s-0034-1378808
• 作为产物：
  描述：

  (S)-N-(cyclopropylmethyl)oripavine ammonium bromide 在 2-甲基十一烷-2-硫醇 、 sodium ethanolate 作用下， 以 二甲基亚砜 为溶剂， 反应 0.92h， 以63%的产率得到N-cyclopropylmethylnororipavine
  参考文献：
  名称：

  谷ip碱季盐的N-去甲基化作用从谷ip碱合成丁丙诺啡

  摘要：

  丁丙诺啡是通过以下顺序从兽皮中合成的，该序列涉及将兽皮中的碳转化为其环丙基甲基季盐，用硫醇盐进行N-脱甲基化为N-环丙基甲基去甲紫罗兰，然后通过先前可获得的方法将该物质转化为标题化合物。新的合成方法避免了以前使用的有毒试剂，时间更短，并且收率相当。提供了所有新化合物的实验数据和光谱数据。

  DOI：

  10.1021/jo200567n

文献信息

• [EN] N-OXIDES OF 4,5-EPOXY-MORPHINANIUM ANALOGS<br/>[FR] N-OXYDES D'ANALOGUES 4,5-ÉPOXY-MORPHINANIUM
  申请人：PROGENICS PHARM INC

  公开号：WO2009067275A1

  公开（公告）日：2009-05-28

  Novel N-oxides of 4,5-epoxy-morphinanIum analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

  揭示了4,5-环氧吗啡啉盐类的新型N-氧化物。还揭示了含有4,5-环氧吗啡啉盐类的N-氧化物的药物组合物，以及它们的药用方法。所揭示的化合物可用作阿片受体调节剂等用途。
• Demethylation of Reticuline and Derivatives Thereof with Fungal Cytochrome P450
  申请人：River Stone Biotech APS

  公开号：US20210230655A1

  公开（公告）日：2021-07-29

  The invention relates to recombinant host cells that expresses one or more genes encoding a cytochrome P450 enzyme capable of N-demethylating and/O-demethylating reticuline and/or derivatives thereof, and also methods of producing a N-demethylated and/or O-demethylated reticuline and/or derivatives thereof, comprising cultivating the recombinant host of the invention in a culture medium under conditions in which the one or more genes encoding the cytochrome P450 enzymes is/are expressed. The reticuline and derivatives thereof are useful for providing access to naturally unavailable and chemically difficult-to-produce starting materials for opioids.

  该发明涉及重组宿主细胞，该细胞表达一个或多个编码细胞色素P450酶的基因，该酶能够对莱角碱和/或其衍生物进行N-去甲基化和/或O-去甲基化，并且还涉及生产N-去甲基化和/或O-去甲基化的莱角碱和/或其衍生物的方法，包括在培养基中培养该发明的重组宿主细胞，在该条件下，编码细胞色素P450酶的一个或多个基因被表达。莱角碱及其衍生物可用于提供自然无法获得和化学上难以生产的阿片类药物的起始物质。
• [EN] PROCESSES FOR THE PREPARATION OF MORPHINANE AND MORPHINONE COMPOUNDS<br/>[FR] PROCÉDÉS POUR LA PRÉPARATION DE COMPOSÉS DE MORPHINANE ET DE MORPHINONE
  申请人：UNIV BROCK

  公开号：WO2010121369A1

  公开（公告）日：2010-10-28

  The present application describes processes for the synthesis of morphinane and morphinone compounds, useful as pharmaceutical agents. Also included are novel intermediates useful in the preparation of these compounds. The process comprises quaternization of oripavine to provide a mixture of the R- and S-isomeric (at the nitrogen) quaternary salts. The R-isomer is readily isolated and converted to various N-(R)-morphinane and N-(S)-morphinone compounds. The R-isomer, S-isomer or a mixture of R- and S-isomers may be demethylated and converted to various morphinane and morphinone compounds.

  本申请描述了合成吗啡烷和吗啡酮化合物的过程，这些化合物可用作药物。还包括在制备这些化合物过程中有用的新型中间体。该过程包括对奥利帕定进行季铵化，以提供R-和S-异构体（在氮上）季铵盐的混合物。R-异构体容易被分离并转化为各种N-(R)-吗啡烷和N-(S)-吗啡酮化合物。R-异构体、S-异构体或R-和S-异构体的混合物可以被去甲基化并转化为各种吗啡烷和吗啡酮化合物。
• [EN] IMPROVED METHOD OF MANUFACTURING BUPRENORPHINE AND ANALOGUES THEREOF FROM ORIPAVINE<br/>[FR] PROCÉDÉ AMÉLIORÉ DE FABRICATION DE BUPRÉNORPHINE ET D'ANALOGUES DE CELLE-CI À PARTIR D'ORIPAVINE
  申请人：SIEGFRIED AG

  公开号：WO2016078833A1

  公开（公告）日：2016-05-26

  The invention relates to an improved method of preparing buprenorphine, a salt thereof, analogues of buprenorphine and their salts. In particular, the invention relates to a method of preparing buprenorphine and related products and salts in economic and ecologic ways having increased yields.

  该发明涉及一种改进的制备丁丙诺啡、其盐、丁丙诺啡类似物及其盐的方法。具体而言，该发明涉及一种以经济和生态方式制备丁丙诺啡及相关产品和盐的方法，其产量增加。
• [EN] PREPARATION OF BUPRENORPHINE<br/>[FR] PRÉPARATION DE BUPRÉNORPHINE
  申请人：EVOLVA SA

  公开号：WO2018211331A1

  公开（公告）日：2018-11-22

  Disclosed are methods for preparing buprenorphine from, for example, compounds such as nororipavine and northebaine.

  公开了从诸如诺罗瑞芭啶和诺吗啡碱等化合物制备丁丙诺啡的方法。