(4R,4aS,7S,7aR,12bS,14S)-7,9-dimethoxy-3-methyl-1,2,3,4,7,7a-hexahydro-4a,7-(epithiomethano)-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carbonitrile

• 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: (4R,4aS,7S,7aR,12bS,14S)-7,9-dimethoxy-3-methyl-1,2,3,4,7,7a-hexahydro-4a,7-(epithiomethano)-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carbonitrile
• 英文别名: (1S,2S,6R,14R,15S,16S)-11,15-dimethoxy-5-methyl-13-oxa-17-thia-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,18-tetraene-16-carbonitrile
• 化学式: C₂₁H₂₂N₂O₃S
• 分子量: 382.483
• InChiKey: ZUMVMKUZTXEHOR-HJCGADSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  80
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7S,7aR,12bS,14S)-7,9-dimethoxy-3-methyl-1,2,3,4,7,7a-hexahydro-4a,7-(epithiomethano)-4,12-methanobenzofuro[3,2-e]isoquinoline-14-carbonitrile 在 三溴化硼 、 2,3-二甲基-1,3-丁二烯 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 24.0h， 生成 奥列巴文
  参考文献：
  名称：

  蒂巴因向鸦片和其他有用中间体的转化，用于半合成阿片类药物：氢吗啡酮的合成

  摘要：

  AbstractThebaine was converted to oripavine in three steps by employing two different modes of protection of the diene moiety; as an iron tricarbonyl complex and as a Diels–Alder adduct with thioformyl cyanide. The two C‐ring‐protected thebaine derivatives were subjected to 3‐O‐demethylation by four different protocols, providing oripavine derivatives, which yielded oripavine after deprotection. Oripavine was then converted to hydromorphone by a three‐step process of ketalization, hydrogenation, and deprotection, without the isolation of intermediates.magnified image

  DOI：

  10.1002/adsc.201400445
• 作为产物：
  描述：

  sodium S-(cyanomethyl) sulfothioate 、 蒂巴因 在 calcium(II) chloride dihydrate 、 三乙胺 作用下， 以 甲醇 、 苯 为溶剂， 反应 8.0h， 以9.6%的产率得到(4R,4aS,7R,7aR,12bR,15R)-7,9-dimethoxy-3-methyl-1,2,3,4,7,7a-hexahydro-7,4a-(epithiomethano)-4,12-methanobenzofuro[3,2-e]isoquinoline-15-carbonitrile
  参考文献：
  名称：

  METHODS FOR THE PREPARATION OF HYDROMORPHONE

  摘要：

  本申请涉及制备吗啡衍生物的方法。具体来说，本申请涉及从鸦片碱制备羟吗啡和从鸦片碱制备鸦啶的方法。

  公开号：

  US20150225419A1

文献信息

• METHODS FOR THE PREPARATION OF HYDROMORPHONE
  申请人：HUDLICKY Tomas

  公开号：US20150225419A1

  公开（公告）日：2015-08-13

  The present application relates to methods for the preparation of morphine derivatives. In particular, the present application relates to methods for the preparation of hydromorphone from oripavine and oripavine from thebaine.

  本申请涉及制备吗啡衍生物的方法。具体来说，本申请涉及从鸦片碱制备羟吗啡和从鸦片碱制备鸦啶的方法。
• US9475823B2
  申请人：——

  公开号：US9475823B2

  公开（公告）日：2016-10-25
• Conversion of Thebaine to Oripavine and Other Useful Intermediates for the Semisynthesis of Opiate-Derived Agents: Synthesis of Hydromorphone
  作者：Brennan Murphy、Ivan Šnajdr、Aleš Machara、Mary Ann A. Endoma-Arias、Theocharis C. Stamatatos、D. Phillip Cox、Tomáš Hudlický

  DOI：10.1002/adsc.201400445

  日期：2014.8.11

  AbstractThebaine was converted to oripavine in three steps by employing two different modes of protection of the diene moiety; as an iron tricarbonyl complex and as a Diels–Alder adduct with thioformyl cyanide. The two C‐ring‐protected thebaine derivatives were subjected to 3‐O‐demethylation by four different protocols, providing oripavine derivatives, which yielded oripavine after deprotection. Oripavine was then converted to hydromorphone by a three‐step process of ketalization, hydrogenation, and deprotection, without the isolation of intermediates.magnified image