(+/-)-(5S,7aS,11aR)-3-hydroxy-5,11a-methano-5,10-dimethyl-7a,8,9,11-tetrahydropyrimidino[5,6-i]benzocyclooctene

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+/-)-(5S,7aS,11aR)-3-hydroxy-5,11a-methano-5,10-dimethyl-7a,8,9,11-tetrahydropyrimidino[5,6-i]benzocyclooctene
• 英文别名: (1S,9R,12R)-9,15-dimethyl-13,15-diazatetracyclo[7.7.1.01,12.03,8]heptadeca-3(8),4,6-trien-6-ol
• 化学式: C₁₇H₂₄N₂O
• 分子量: 272.39
• InChiKey: AFTHUEYDCBUGFM-BRWVUGGUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  35.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-(5S,7aS,11aR)-3-hydroxy-5,11a-methano-5,10-dimethyl-7a,8,9,11-tetrahydropyrimidino[5,6-i]benzocyclooctene 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 36.0h， 以81%的产率得到(1R,9S,10R)-10-amino-1-methyl-9-(methylaminomethyl)tricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol
  参考文献：
  名称：

  Asymmetric Syntheses, Opioid Receptor Affinities, and Antinociceptive Effects of 8-Amino-5,9-methanobenzocyclooctenes, a New Class of Structural Analogues of the Morphine Alkaloids

  摘要：

  Several 8-amino-5,9-methanobenzocyclooctenes have been prepared by asymmetric organic synthesis techniques. Opioid receptor affinity studies have revealed the virtual absence of enantioselectivity for receptor binding, particularly at the mu-receptor, for the (+)-3a-f and the (-)-3a-f series. It is noteworthy that inversion of configuration at the nitrogen-bearing carbon atom [(5S,8S,9S)-8-amino-3-hydroxy-5,9-methano-9-(methoxymethyl)-5-methylbenzocyclooctene, (+)-3a vs (5S,8S,9R)-8-amino-3-hydroxy-5,9-methanoxymethyl)-5-methylbenzocyclooctene, (dl)-22] resulted in a >10-fold increase in kappa-receptor affinity. Antinociceptive studies demonstrated that (dl)-22 was a full kappa-agonist while (+)-3a and (-)-3a did not possess kappa-activity. Although both (dl)-22 and (+)-3a/(-)-3a had high affinity for the mu-receptor, these compounds did not act as high-affinity agonists or antagonists at this receptor.

  DOI：

  10.1021/jm950817g
• 作为产物：
  描述：

  3,6-dimethyl-1H-quinazoline-2,4-dione 在 lithium aluminium tetrahydride 、 间戊二烯 、 三氟甲磺酸 、 氨 、 叔丁醇 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.58h， 生成 (+/-)-(5S,7aS,11aR)-3-hydroxy-5,11a-methano-5,10-dimethyl-7a,8,9,11-tetrahydropyrimidino[5,6-i]benzocyclooctene
  参考文献：
  名称：

  Asymmetric Syntheses, Opioid Receptor Affinities, and Antinociceptive Effects of 8-Amino-5,9-methanobenzocyclooctenes, a New Class of Structural Analogues of the Morphine Alkaloids

  摘要：

  Several 8-amino-5,9-methanobenzocyclooctenes have been prepared by asymmetric organic synthesis techniques. Opioid receptor affinity studies have revealed the virtual absence of enantioselectivity for receptor binding, particularly at the mu-receptor, for the (+)-3a-f and the (-)-3a-f series. It is noteworthy that inversion of configuration at the nitrogen-bearing carbon atom [(5S,8S,9S)-8-amino-3-hydroxy-5,9-methano-9-(methoxymethyl)-5-methylbenzocyclooctene, (+)-3a vs (5S,8S,9R)-8-amino-3-hydroxy-5,9-methanoxymethyl)-5-methylbenzocyclooctene, (dl)-22] resulted in a >10-fold increase in kappa-receptor affinity. Antinociceptive studies demonstrated that (dl)-22 was a full kappa-agonist while (+)-3a and (-)-3a did not possess kappa-activity. Although both (dl)-22 and (+)-3a/(-)-3a had high affinity for the mu-receptor, these compounds did not act as high-affinity agonists or antagonists at this receptor.

  DOI：

  10.1021/jm950817g

文献信息

• Asymmetric Syntheses, Opioid Receptor Affinities, and Antinociceptive Effects of 8-Amino-5,9-methanobenzocyclooctenes, a New Class of Structural Analogues of the Morphine Alkaloids
  作者：Arthur G. Schultz、Aihua Wang、Carlos Alva、Alice Sebastian、Stanley D. Glick、Darlene C. Deecher、Jean M. Bidlack

  DOI：10.1021/jm950817g

  日期：1996.1.1

  Several 8-amino-5,9-methanobenzocyclooctenes have been prepared by asymmetric organic synthesis techniques. Opioid receptor affinity studies have revealed the virtual absence of enantioselectivity for receptor binding, particularly at the mu-receptor, for the (+)-3a-f and the (-)-3a-f series. It is noteworthy that inversion of configuration at the nitrogen-bearing carbon atom [(5S,8S,9S)-8-amino-3-hydroxy-5,9-methano-9-(methoxymethyl)-5-methylbenzocyclooctene, (+)-3a vs (5S,8S,9R)-8-amino-3-hydroxy-5,9-methanoxymethyl)-5-methylbenzocyclooctene, (dl)-22] resulted in a >10-fold increase in kappa-receptor affinity. Antinociceptive studies demonstrated that (dl)-22 was a full kappa-agonist while (+)-3a and (-)-3a did not possess kappa-activity. Although both (dl)-22 and (+)-3a/(-)-3a had high affinity for the mu-receptor, these compounds did not act as high-affinity agonists or antagonists at this receptor.