dihydropseudocodeinone | 5056-91-7

• 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: dihydropseudocodeinone
• 英文别名: Dihydropseudocodeinon；4,5α-epoxy-3-methoxy-17-methyl-morphinan-8-one；4,5α-Epoxy-3-methoxy-17-methyl-morphinan-8-on；(4R,4aR,7aS,12bS)-9-methoxy-3-methyl-1,2,4,4a,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-5-one
• CAS: 5056-91-7
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: YIYGKSBUPPUBEW-FRYJOBKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dihydropseudocodeinone 在 盐酸 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 50.0h， 生成 4,5α-epoxy-3-methoxy-8-oxomorphinan
  参考文献：
  名称：

  Synthesis and .delta.-Opioid Receptor Antagonist Activity of a Naltrindole Analog with a Regioisomeric Indole Moiety

  摘要：

  Indolomorphinans 2 and 3, in which the indole moiety is fused to the 7,8-position of the morphinan system, have been synthesized from dihydropseudocodeinone 4 and evaluated for antagonist activity on the mouse vas deferens (MVD) and guinea pig ileum (GPI) preparations. Indolomorphinan 2 was found to be similar to 1/60th as potent as naltrindole 1 in the MVD and an agonist in the GPI preparation. A comparable difference in affinity between 1 and 2 was observed. The methyl analogue 3 was inactive in both preparations. The results of this study support the idea that the regio orientation of the indolic benzene moiety of 1 is optimal for delta-opioid receptor antagonist activity. It is proposed that the proper alignment of the benzene moiety with an address subsite on the delta receptor is critical for potent delta antagonist activity.

  DOI：

  10.1021/jm00038a019
• 作为产物：
  描述：

  4,5α-epoxy-3-methoxy-17-methyl-8α-(toluene-4-sulfonyloxy)-(14α)-morphinane 在 2,4,6-三甲基吡啶 、 二苯甲酮 、 potassium tert-butylate 作用下， 以 苯 为溶剂， 反应 3.5h， 生成 dihydropseudocodeinone
  参考文献：
  名称：

  Synthesis of a B/C trans-fused Morphine Structure

  摘要：

  Δ8-去氧可待因（I）经氢硼化反应得到 B/C 反式融合吗啡衍生物 (-)-3-甲氧基-8α-羟基-4，5α-氧-N-甲基异吗啡南（III）以及两种次要产物二氢假可待因 （IV）和 VII。III 与对甲苯磺酰氯反应生成 8-对甲苯磺酸盐（Vc），Vc 与氢化锂铝处理后生成 (-)-3-甲氧基-4, 5α-oxy-N-methylisomorphinan (VII)。Vc 与 2，4，6-甲苯胺发生消除反应，得到两种双键异构体 I 和 3-甲氧基-4，5α-氧-Δ7-N-甲基异吗啡南（XII）。I 经氢化可得到已知的二氢去氧可待因（XIII）。XII 加氢后得到 B/C 反式异构体 VII。对氢化产物（III）及其衍生物进行了一些额外的研究，以支持 B/C 反式五环结构。

  DOI：

  10.1248/cpb.13.1422

文献信息

• THE PREPARATION OF SOME DIHYDRO KETONES IN THE MORPHINE SERIES BY OPPENAUER OXIDATION
  作者：HENRY RAPOPORT、ROBERT NAUMANN、EUGENE R. BISSELL、ROBERT M. BONNER

  DOI：10.1021/jo01151a029

  日期：1950.9
• Reduction Studies in the Morphine Series. VII. Pseudocodeinone¹
  作者：Robert E. Lutz、Lyndon Small

  DOI：10.1021/ja01315a096

  日期：1935.12
• Synthesis of a B/C trans-fused Morphine Structure
  作者：Hiroshi Kugita、Mikio Takeda

  DOI：10.1248/cpb.13.1422

  日期：——

  Hydroboration of Δ8-desoxycodeine (I) gave a B/C trans-fused morphine derivative, (-)-3-methoxy-8α-hydroxy-4, 5α-oxy-N-methylisomorphinan (III) along with two minor products, dihydropseudocodeine (IV) and VII. III, by reaction with p-toluenesulfonyl-chloride gave the 8-p-toluenesulfonate (Vc), which was treated with lithiun aluminum hydride to give (-)-3-methoxy-4, 5α-oxy-N-methylisomorphinan (VII). Elimination reaction of Vc with 2, 4, 6-collidine afforded two double-bond isomers, I and 3-methoxy-4, 5α-oxy-Δ7-N-methylisomorphinan (XII). I gave on hydrogenation the known dihydrodesoxycodeine (XIII). Hydrogenation of XII gave the B/C trans isomer, VII. Some additional studies were made on the hydroboration product (III) and its derivatives to support the B/C trans pentacyclic structure.

  Δ8-去氧可待因（I）经氢硼化反应得到 B/C 反式融合吗啡衍生物 (-)-3-甲氧基-8α-羟基-4，5α-氧-N-甲基异吗啡南（III）以及两种次要产物二氢假可待因 （IV）和 VII。III 与对甲苯磺酰氯反应生成 8-对甲苯磺酸盐（Vc），Vc 与氢化锂铝处理后生成 (-)-3-甲氧基-4, 5α-oxy-N-methylisomorphinan (VII)。Vc 与 2，4，6-甲苯胺发生消除反应，得到两种双键异构体 I 和 3-甲氧基-4，5α-氧-Δ7-N-甲基异吗啡南（XII）。I 经氢化可得到已知的二氢去氧可待因（XIII）。XII 加氢后得到 B/C 反式异构体 VII。对氢化产物（III）及其衍生物进行了一些额外的研究，以支持 B/C 反式五环结构。
• Synthesis and .delta.-Opioid Receptor Antagonist Activity of a Naltrindole Analog with a Regioisomeric Indole Moiety
  作者：P. S. Portoghese、S. Ohkawa、S. T. Moe、A. E. Takemori

  DOI：10.1021/jm00038a019

  日期：1994.6

  Indolomorphinans 2 and 3, in which the indole moiety is fused to the 7,8-position of the morphinan system, have been synthesized from dihydropseudocodeinone 4 and evaluated for antagonist activity on the mouse vas deferens (MVD) and guinea pig ileum (GPI) preparations. Indolomorphinan 2 was found to be similar to 1/60th as potent as naltrindole 1 in the MVD and an agonist in the GPI preparation. A comparable difference in affinity between 1 and 2 was observed. The methyl analogue 3 was inactive in both preparations. The results of this study support the idea that the regio orientation of the indolic benzene moiety of 1 is optimal for delta-opioid receptor antagonist activity. It is proposed that the proper alignment of the benzene moiety with an address subsite on the delta receptor is critical for potent delta antagonist activity.