(6aR,10aR)-3-(1,1-Dimethyl-heptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol

• 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: (6aR,10aR)-3-(1,1-Dimethyl-heptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol
• 英文别名: (6aR,10aR)-3-(1',1'-dimethylheptyl)-Δ⁸-tetrahydrocannabinol；HU-208；3-(1',1'-dimethylheptyl)-Δ8-tetrahydrocannabinol；(6Ar,10ar)-3-(1,1-dimethylheptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-dibenzo[b,d]pyran-1-ol；(6aR,10aR)-6,6,9-trimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol
• 化学式: C₂₅H₃₈O₂
• 分子量: 370.576
• InChiKey: PJPBVOAEXHKPAB-WOJBJXKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (6aR,10aR)-3-(1,1-Dimethyl-heptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol 在 SIBX 作用下， 以 乙酸乙酯 为溶剂， 反应 18.0h， 以54%的产率得到3’-depentyl-3’-(α,α-dimethylheptyl)-ortho-Δ8-tetrahydrocannabinol quinone
  参考文献：
  名称：

  邻和对大麻酚醌的区域发散合成

  摘要：

  后氧化prototropic-和价互变异构平衡负责的只形成p -quinones在λ 5大麻素-iodane氧化。O-甲基化可防止质子平衡，并且通过互补的氧化和甲基化步骤，可以得到异构的邻-和对-大麻醌。

  DOI：

  10.1002/ejoc.202001258
• 作为产物：
  描述：

  5-(1,1-二甲基庚基)间苯二酚 、 (4R)-1-甲基-4-(1-甲基乙烯)-2-环己烯-1-醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 (6aR,10aR)-3-(1,1-Dimethyl-heptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol
  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

文献信息

• 3-(1′,1′-Dimethylbutyl)-1-deoxy-Δ8-THC and related compounds: synthesis of selective ligands for the CB2 receptor
  作者：John W. Huffman、John Liddle、Shu Yu、Mie Mie Aung、Mary E. Abood、Jenny L. Wiley、Billy R. Martin

  DOI：10.1016/s0968-0896(99)00219-9

  日期：1999.12

  and CB2 receptors were determined employing previously described procedures. Five of the 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 1-5) have high affinity (Ki = < 20 nM) for the CB2 receptor. Four of them (2, n = 1-4) also have little affinity for the CB1 receptor (Ki = > 295 nM). 3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC (2, n = 2) has very high affinity for the CB2 receptor (Ki

  描述了15个1-deoxy-delta8-THC类似物的合成和药理作用，其中一些对CB2受体具有高亲和力。所述脱氧大麻素包括1-脱氧-11-羟基-δ8-THC（5），1-脱氧δ8-THC（6），1-脱氧-3-丁基-δ8-THC（7），1-脱氧-3 -hexyl-delta8-THC（8）和一系列3-（1'，1'-二甲基烷基）-1-deoxy-delta8-THC类似物（2，n = 0-4，6，7，其中n =侧链中的碳原子数-2）。还制备了脱氧萘丁酮（16）的三种衍生物（17-19）。使用前述方法确定每种化合物对CB1和CB2受体的亲和力。3-（1'，1'-二甲基烷基）-1-脱氧-delta8-THC类似物中的五个（2，n = 1-5）对CB2受体具有高亲和力（Ki = <20 nM）。其中四个（2，n = 1-4）对CB1受体的亲和力也很小（Ki => 295 nM）。3-（1'，1'-二
• Novel Cannabinol Probes for CB1 and CB2 Cannabinoid Receptors
  作者：Anu Mahadevan、Craig Siegel、Billy R. Martin、Mary E. Abood、Irina Beletskaya、Raj K. Razdan

  DOI：10.1021/jm0001572

  日期：2000.10.1

  CBN-3-(1',1'-dimethylheptyl) analogues were prepared by sulfur dehydrogenation of Delta(8)-THC-3-(1',1'-dimethylheptyl) analogues. 9-Substituted CBN analogues were prepared by the standard sulfur dehydrogenation of 9-substituted Delta(8)-THC analogues (Scheme 1), which in turn were prepared following our previous procedure using selenium dioxide oxidation of the corresponding Delta(8)-THCs followed by sodium

  THCs的酚羟基对于与CB1受体结合很重要，但对与CB2受体结合却不那么重要的发现促使我们将这一发现扩展到大麻酚（CBN）系列。为了研究CBN类似物的SAR，选择了在C-1，C-3和C-9位置具有取代基的CBN衍生物，因为这些位置在THC的SAR中起着关键作用。CBN-3-（1'，1'-二甲基庚基）类似物是通过Delta（8）-THC-3-（1'，1'-二甲基庚基）类似物的硫脱氢制备的。通过9-取代的Delta（8）-THC类似物的标准硫脱氢反应制备9-取代的CBN类似物（方案1），依次按照我们先前的步骤进行制备，使用相应的Delta（8）-THC的二氧化硒氧化，再用亚氯酸钠氧化，得到9-羧基-Delta（8）-THC衍生物。通过用LiAlH（4）还原从相应的9-羰甲氧基-CBN类似物制备11-羟基-CBN类似物。脱氧-CBN类似物14由相应的Delta（8）-THC类似物11制备，方法是
• NOVEL ARYLATED CAMPHENES, PROCESSES FOR THEIR PREPARATION AND USES THEREOF
  申请人：Mechoulam Raphael

  公开号：US20120245366A1

  公开（公告）日：2012-09-27

  The present invention relates to arylated camphenes, processes for their preparation and uses thereof for the manufacture of medicaments for the treatment of diseases, disorders or conditions associated with, or benefiting from stimulation of CB2 receptors.

  本发明涉及芳基化萜烯、其制备方法以及用于制造治疗与CB2受体刺激有关的疾病、紊乱或状况的药物的用途。
• Catalytic asymmetric synthesis of cannabinoids and menthol from neral
  作者：Joyce A. A. Grimm、Hui Zhou、Roberta Properzi、Markus Leutzsch、Giovanni Bistoni、Johanna Nienhaus、Benjamin List

  DOI：10.1038/s41586-023-05747-9

  日期：2023.3.23

  The selective conversion of natural or synthetic neral to (1R,6S)-trans-isopiperitenol would enable and expedite sustainable routes to menthol^1,2 and cannabinoids^3–5. However, this reaction has been considered impossible because its product is more reactive to the required acid catalysts than its starting material, resulting in several side products^6–9. We now show that an unsymmetric, strong and confined chiral acid, a highly fluorinated imino-imidodiphosphate, catalyses this process with excellent efficiency and selectivity. Expanding the method to other α,β-unsaturated aldehydes could enable access to new cannabinoids and menthol derivatives not readily accessible previously. Mechanistic studies suggest that the confined catalyst accomplishes this reaction by binding the product in an unreactive conformation, thereby preventing its decomposition. We also show how (1R,6S)-trans-isopiperitenol can be readily converted to pharmaceutically useful cannabinoids and menthol, each in the shortest and most atom-economic routes so far.

  摘要将天然或合成的矿物质选择性地转化为 (1R,6S)-反式-异哌啶烯醇，可以实现并加快薄荷醇1,2 和大麻素3-5 的可持续路线。然而，这一反应一直被认为是不可能的，因为其产物对所需酸催化剂的反应性比起始原料要强，会产生多种副产品6-9。现在，我们证明了一种不对称、强限制性手性酸（一种高度氟化的亚氨基-亚胺二磷酸酯）可以催化这一过程，并具有极佳的效率和选择性。将这种方法扩展到其他α、β-不饱和醛类，可以获得以前不容易获得的新大麻素和薄荷醇衍生物。机理研究表明，密闭催化剂是通过将产物束缚在非反应构象中，从而阻止其分解来完成这一反应的。我们还展示了 (1R,6S)-反式-异哌替苯酚如何以迄今为止最短和最经济的途径，轻易地转化为具有药用价值的大麻素和薄荷醇。
• 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。