11-oxo-(6aR,10aR)-3-(1',1'-dimethylheptyl)-Δ⁸-tetrahydrocannabinol 1-O-acetate | 305833-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 11-oxo-(6aR,10aR)-3-(1',1'-dimethylheptyl)-Δ⁸-tetrahydrocannabinol 1-O-acetate
• CAS: 305833-23-2
• 化学式: C₂₇H₃₈O₄
• 分子量: 426.59
• InChiKey: ZQQIPZGMGQNZLR-FGZHOGPDSA-N

物化性质

• 沸点：
  508.0±50.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.65
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  11-oxo-(6aR,10aR)-3-(1',1'-dimethylheptyl)-Δ⁸-tetrahydrocannabinol 1-O-acetate 在 双氧水 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 18.0h， 生成 (6aR,10aR)-1-acetoxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-9-carboxylic acid
  参考文献：
  名称：

  Ultrapure ajulemic acid has improved CB2 selectivity with reduced CB1 activity

  摘要：

  Ajulemic acid, a side-chain analog of Delta(8)-THC-11-oic acid, was designed as a potent therapeutic agent free of the psychotropic adverse effects typical of most cannabinoids. Subsequent studies of ajulemic acid have yielded widely divergent findings on the occurrence of these adverse effects. To help resolve these discrepancies, we have prepared highly purified ajulemic acid using a different synthetic method than previously reported in the literature and compared its cannabinoid receptor binding constants with those obtained using several other preparations from different sources. Whereas CB2 binding did not vary greatly among all of the samples, the CB1 binding showed a wide range of affinities. The highly purified product (JBT-101) reported here had the weakest affinity for CB1 while the original preparation (HU-239) showed the strongest affinity for CBI. The CB1/CB2 ratio of affinities was 12.3 for JBT-101 whereas that for HU-239 was 0.19, a 65-fold difference. Functional responses such as catalepsy and hypothermia using JBT-101 versus HU-239 displayed reduced CB1 activity in keeping with the receptor binding data. Thus, earlier conclusions on the limited therapeutic index for ajulemic acid need to be reconsidered in the light of the data now obtained using JBT-101. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.062
• 作为产物：
  描述：

  3-(1,1-Dimethyl-heptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol 生成 11-oxo-(6aR,10aR)-3-(1',1'-dimethylheptyl)-Δ⁸-tetrahydrocannabinol 1-O-acetate
  参考文献：
  名称：

  Bioorg. Med. Chem. 2014, 22, 3245-3251

  摘要：

  DOI：

文献信息

• Syntheses of Cannabinoid Metabolites: Ajulemic Acid and HU-210
  作者：Wenbin Shao、Pingyong Liao、Xiaoyan Zhang、Binbin Fan、Ruijia Chen、Xilong Chen、Xuejun Zhao、Wenbin Liu

  DOI：10.3390/molecules29020526

  日期：——

  Cannabinoid metabolites have been reported to be more potent than their parent compounds. Among them, ajulemic acid (AJA) is a side-chain analog of Δ9-THC-11-oic acid, which would be a good template structure for the discovery of more potent analogues. Herein, we optimized the key allylic oxidation step to introduce the C-11 hydroxy group with a high yield. A series of compounds was prepared with this

  据报道，大麻素代谢物比其母体化合物更有效。其中，ajulemic acid （AJA） 是 Δ9-THC-11-oic acid 的侧链类似物，这将是发现更有效类似物的良好模板结构。在此，我们优化了关键的烯丙基氧化步骤，以高产率引入 C-11 羟基。在此条件下制备了一系列化合物，包括 胡-210、11-nor-Δ8-四氢大麻酚 （THC）-羧酸和 Δ9-THC-羧酸。
• [EN] ULTRAPURE TETRAHYDROCANNABINOL-11-OIC ACIDS<br/>[FR] ACIDES TÉTRAHYDROCANNABINOL-11-OÏQUES ULTRAPURS
  申请人：CORBUS PHARMACEUTICALS INC

  公开号：WO2014127016A3

  公开（公告）日：2015-11-26