(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-3-methyl-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-9-olate;hydrochloride | 693784-16-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-3-methyl-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-9-olate;hydrochloride
• CAS: 693784-16-6
• 化学式: C₂₁H₂₆NO₄*Cl
• 分子量: 391.895
• InChiKey: MWMNPLRPPPCUAA-KNLJMPJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.33
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-3-methyl-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-9-olate;hydrochloride 在 Dowex-1 resin (strongly basic bromine loaded, 50-100 mesh) 作用下， 以 甲醇 、 水 为溶剂， 生成 (S)-N-Methylnaltrexone bromide 、 (R)-methylnaltrexone bromide
  参考文献：
  名称：

  [EN] PROCESSES FOR THE PREPARATION OF MORPHINANE AND MORPHINONE COMPOUNDS
  [FR] PROCÉDÉS POUR LA PRÉPARATION DE COMPOSÉS DE MORPHINANE ET DE MORPHINONE

  摘要：

  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。

  公开号：

  WO2010121369A1

文献信息

• Processes for the Preparation of Morphinane and Morphinone Compounds
  申请人：Hudlicky Tomas

  公开号：US20120046465A1

  公开（公告）日：2012-02-23

  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中有用的新型中间体。该过程包括对烟阔叶芥子碱进行季铵化，以提供R-和S-异构体（在氮上）季铵盐的混合物。R-异构体易于分离并转化为各种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去甲基化并转化为各种吗啡烷和吗啡酮化合物。
• Processes for the preparation of morphinane and morphinone compounds
  申请人：Hudlicky Tomas

  公开号：US08853401B2

  公开（公告）日：2014-10-07

  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.

  本申请描述了用作药物的吗啡烷和吗啡酮化合物的合成过程。还包括在制备这些化合物中有用的新型中间体。该过程包括将欧比芬季铵化以提供R-和S-异构（在氮上）季铵盐的混合物。R-异构体易于分离并转化为各种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去甲基化并转化为各种吗啡烷和吗啡酮化合物。
• Synthesis of Naltrexone and (R)-Methylnaltrexone from Oripavine via Direct Oxidation of Its Quaternary Salts
  作者：Tomas Hudlicky、Ales Machara、Lukas Werner、Hannes Leisch、Robert Carroll、David Adams、D. Haque、D. Cox

  DOI：10.1055/s-0034-1378808

  日期：——

  (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.