8-epi-salvinorin A | 844841-26-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 8-epi-salvinorin A
• 英文别名: C-8-epi-salvinorin A；Episalvinorin A；(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester；Salvinorin A (ester)；methyl (2S,4aS,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
• CAS: 844841-26-5
• 化学式: C₂₃H₂₈O₈
• 分子量: 432.471
• InChiKey: OBSYBRPAKCASQB-FBCTZMOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-epi-salvinorin A 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以67%的产率得到8-epi-deacetyl-1,10-didehydrosalvinorin G
  参考文献：
  名称：

  Revised structure of deacetyl-1,10-didehydrosalvinorin G

  摘要：

  In comparison with the NMR data of salvinorin A and its 8-epimer, the published structure of deacetyl-1,10-didehydrosalvinorin G was revised to its 8-epimer. The stereochernistry of 8-epi-deacetyl-1,10-didehydrosalvinorin G was further confirmed by NOESY and chemical synthesis. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.05.179
• 作为产物：
  描述：

  丹酚 A 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 氘代乙腈 为溶剂， 生成 8-epi-salvinorin A
  参考文献：
  名称：

  O6C-20-nor-salvinorin A是一种稳定有效的KOR激动剂

  摘要：

  Salvinorin A（SalA）是κ阿片受体（KOR）的有效选择性激动剂，但其不稳定性使药物化学工作受挫。用弱碱（如DBU）处理SalA会导致C8差向异构化，并丧失受体亲和力和信号传导能力。在这里，我们显示了用H替换C20和用CH 2替换O6相对于其C8差向异构体稳定了SalA支架，以至于完全抑制了差向异构化。这种新化合物O6C-20-nor-SalA对KOR的激动作用保留了很高的效力。

  DOI：

  10.1016/j.bmcl.2018.01.055

文献信息

• Neoclerodane Diterpenes as a Novel Scaffold for μ Opioid Receptor Ligands
  作者：Wayne W. Harding、Kevin Tidgewell、Nathan Byrd、Howard Cobb、Christina M. Dersch、Eduardo R. Butelman、Richard B. Rothman、Thomas E. Prisinzano

  DOI：10.1021/jm048963m

  日期：2005.7.1

  Structural modification of salvinorin A, the active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study a nonnitrogenous neoclerodane diterpene with mu opioid receptor affinity (13) that is an agonist at mu opioid receptors. This represents the identification of a novel structural class of

  Salvinorin A（Salvia divinorum的活性成分）的结构修饰已导致合成了具有阿片受体亲和力和活性的新型新环戊烷二萜。我们在这项研究中报告了一种非氮新环戊二烯双萜，具有μ阿片受体的亲和力（13），是μ阿片受体的激动剂。这代表了对μ阿片样物质受体激动剂的新型结构类别的鉴定。
• Novel neoclerodane diterpene derivatives from the smoke of salvinorin A
  作者：Zhongze Ma、Gang Deng、David Y.W. Lee

  DOI：10.1016/j.tetlet.2010.07.144

  日期：2010.9

  Salvinorin A is a naturally occurring potent and selective kappa opioid receptor agonist, and smoking salvinorin A produces the most intense hallucinogenic effects in human. Eight neoclerodane diterpene derivatives were isolated from the smoke of salvinorin A, and their structures were identified by spectroscopic methods. The major structural changes include epimerizations, eliminations, and rearrangements

  Salvinorin A 是一种天然存在的强效选择性κ阿片受体激动剂，吸烟 Salvinorin A 对人类产生最强烈的致幻作用。从 Salvinorin A 的烟雾中分离出 8 种新克莱罗丹二萜衍生物，并通过光谱方法对其结构进行了鉴定。主要的结构变化包括差向异构化、消除和重排。
• Studies toward the Pharmacophore of Salvinorin A, a Potent κ Opioid Receptor Agonist
  作者：Thomas A. Munro、Mark A. Rizzacasa、Bryan L. Roth、Beth A. Toth、Feng Yan

  DOI：10.1021/jm049438q

  日期：2005.1.1

  Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective K opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors.
• Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues
  作者：David Y.W. Lee、Vishnu V.R. Karnati、Minsheng He、Lee-Yuan Liu-Chen、Leelakrishna Kondaveti、Zhongze Ma、Yulin Wang、Yong Chen、Cecile Beguin、William A. Carlezon、Bruce Cohen

  DOI：10.1016/j.bmcl.2005.05.048

  日期：2005.8

  Salvinorin A is the most potent naturally occurring opioid agonist yet discovered with high selectivity and affinity for kappa-opioid receptor. To explore its structure and activity relationships, a series of salvinorin A derivatives modified at the C(2) position were prepared and studied. These salvinorin A derivatives were screened for binding and functional activities at the human K-opioid receptor. Compound 4, containing a methoxymethyl group at the 2-position, was a full kappa-agonist with an EC50 value at 0.6 nM, which is about 7 times more potent than salvinorin A. (c) 2005 Elsevier Ltd. All rights reserved.
• Revised structure of deacetyl-1,10-didehydrosalvinorin G
  作者：Zhongze Ma、David Y.W. Lee

  DOI：10.1016/j.tetlet.2007.05.179

  日期：2007.7

  In comparison with the NMR data of salvinorin A and its 8-epimer, the published structure of deacetyl-1,10-didehydrosalvinorin G was revised to its 8-epimer. The stereochernistry of 8-epi-deacetyl-1,10-didehydrosalvinorin G was further confirmed by NOESY and chemical synthesis. (c) 2007 Elsevier Ltd. All rights reserved.