14β-hydroxycodeinone

• 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: 14β-hydroxycodeinone
• 英文别名: 14-β-Hydroxycodeinon；4,5α-epoxy-14-hydroxy-3-methoxy-17-methyl-morphin-7-en-6-one；(4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• 化学式: C₁₈H₁₉NO₄
• 分子量: 313.353
• InChiKey: YYCRAERBSFHMPL-XIAUJNHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  14β-hydroxycodeinone 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、303.98 kPa 条件下， 反应 28.17h， 生成 14β-methoxy-7,8-dihydrocodeinone
  参考文献：
  名称：

  Common anionic receptor site hypothesis: its relevance to the antagonist action of naloxone

  摘要：

  Appropriate modification of 14 beta-methoxy- and 14 beta-ethoxycodeinone (prepared by alkylation of 14 beta-hydroxycodeinone) has generated four alkoxy analogues (3a-d) of naloxone and naltrexone. These agents were pure narcotic antagonists in contradiction to the predictions of the common anionic receptor site hypothesis, postulated to be of importance in the enhanced antagonism of naloxone. The molecular change from allyl to cyclopropylmethyl on the N atom increased selectivity of these antagonists for the mu receptor to the same extent as found for naloxone. Increase in the length of the C14 O-substituent had no effect on receptor selectivity, and either formation in most cases did not significantly alter oral/parenteral ratios of durations of action.

  DOI：

  10.1021/jm00344a005
• 作为产物：
  描述：

  oxycodeinone N-oxide hydrochloride 以 异丙醇 为溶剂， 反应 17.0h， 以62%的产率得到N-noroxycodeinone
  参考文献：
  名称：

  [EN] A METHOD FOR THE N-DEMETHYLATION OF N-METHYL HETEROCYCLES
  [FR] PROCÉDÉ POUR LA N-DÉMÉTHYLATION DE N-MÉTHYL-HÉTÉROCYCLES

  摘要：

  本发明提供了使用氧化态为零的过渡金属、二茂铁或其取代衍生物，或Cr 3+ 对N-去甲基化、N-甲基化杂环和N-甲基、N-氧化物杂环的方法。本发明方法制备的N-去甲基化杂环也被提供。

  公开号：

  WO2011032214A1

文献信息

• CONVERSION OF THEBAINE TO MORPHINE DERIVATIVES
  申请人：Carroll Robert James

  公开号：US20090005563A1

  公开（公告）日：2009-01-01

  The present invention provides methods for the conversion of thebaine to a morphine derivative, such as hydrocodone. Novel ketal intermediates of the conversion are provided. A one-pot procedure for the conversion comprises treating thebaine with an acid in the presence of a metal catalyst.

  本发明提供了将吗啡碱转化为吗啡衍生物（如羟考酮）的方法。提供了该转化的新型缩酮中间体。该转化的一锅法包括在金属催化剂存在下用酸处理吗啡碱。
• SYNTHESIS OF OXYCODONE HYDROCHLORIDE
  申请人：Cody Laboratories, Inc.

  公开号：US20150166553A1

  公开（公告）日：2015-06-18

  Synthetic methods are provided for preparation of oxycodone and salts thereof with an improved impurity profile. Thebaine is converted to 14-hydroxycodeinone sulfate intermediate to minimize a 7,8-dihydro-8,14-dihydroxycodeinone impurity. Efficient methods for conversion of oxycodone base to oxycodone hydrochloride are provided to minimize 14-hydroxycodeinone impurity in the final product.

  提供了一种合成方法，用于制备氧可酮及其盐，具有改进的杂质特性。 将橙皮碱转化为14-羟基可待因酮硫酸盐中间体，以减少7,8-二氢-8,14-二羟基可待因酮的杂质。 提供了将氧可酮碱转化为氧可酮盐酸盐的高效方法，以减少最终产品中的14-羟基可待因酮杂质。
• CONVERSION OF OXYCODONE BASE TO OXYCODONE HYDROCHLORIDE
  申请人：Cody Laboratories, Inc.

  公开号：US20150166552A1

  公开（公告）日：2015-06-18

  Synthetic methods are provided for preparation of oxycodone and salts thereof with an improved impurity profile. Thebaine is converted to 14-hydroxycodeinone sulfate intermediate to minimize a 7,8-dihydro-8,14-dihydroxycodeinone impurity. Efficient methods for conversion of oxycodone base to oxycodone hydrochloride are provided to minimize 14-hydroxycodeinone impurity in the final product.

  提供了合成方法，用于制备盐酸氧可酮及其改进的杂质谱。将蒂巴因转化为14-羟基可待因酮硫酸盐中间体，以最小化7,8-二氢-8,14-二羟基可待因酮杂质。提供了将氧可酮碱转化为盐酸氧可酮的高效方法，以最小化最终产品中的14-羟基可待因酮杂质。
• Process For Preparing Oxycodone Having Reduced Levels Of 14-Hydroxycodeinone
  申请人：Cox D. Phillip

  公开号：US20080139814A1

  公开（公告）日：2008-06-12

  The present invention is directed to processes for preparing oxycodone base and oxycodone hydrochloride compositions having less than 10 ppm of 14-hydroxycodeinone.

  本发明涉及制备盐酸羟考酮和盐酸羟考酮组合物的方法，其含有少于10 ppm的14-羟基可待因。
• Process for Reducing Impurities in Oxycodone Base
  申请人：Cox D. Phillip

  公开号：US20080132703A1

  公开（公告）日：2008-06-05

  The present invention is directed to a process for using n-butanol to prepare an oxycodone base compositions having reduced levels of impurities such as 14-hydroxycodeinone and DHDHC.

  本发明涉及使用正丁醇制备含有较低杂质水平（如14-羟基可待因和DHDHC）的氧考酮基础组合物的方法。