C-2-epi-salvinorin B | 865438-59-1

• 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: C-2-epi-salvinorin B
• 英文别名: methyl (13S,1R,4R,6R,7R)-13-(3-furyl)-4-hydroxy-1,7-dimethyl-12-oxa-3,11-dioxotricyclo[8.4.0.0(2,7)]tetradecane-6-carboxylate；epi-salvinorin B；methyl (2S,4aR,6aR,7R,9R,10aS,10bR)-2-(furan-3-yl)-9-hydroxy-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
• CAS: 865438-59-1
• 化学式: C₂₁H₂₆O₇
• 分子量: 390.433
• InChiKey: BLTMVAIOAAGYAR-GKRPYSMHSA-N

物化性质

• 熔点：
  241 °C
• 沸点：
  562.8±50.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  C-2-epi-salvinorin B 在 吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-(2-propyl)-2-amino salvinorin B
  参考文献：
  名称：

  Synthesis and in vitro evaluation of salvinorin A analogues: Effect of configuration at C(2) and substitution at C(18)

  摘要：

  kappa-opioid receptor ligands have raised interest for their apparent effects on mood. The potent and selective kappa-agonist salvinorin A has short-lasting (15 min) depressive-like effects in rats in behavioral models used to study mood disorders. Two series of salvinorin derivatives modified at C(2) and C(18), respectively, were synthesized and their kappa-opioid receptor affinities, potencies, and efficacies were evaluated using in vitro receptor binding and biochemical functional assays. Modification at C(2) yielded potent kappa-agonists that are predicted to have improved metabolic stability (14a, 15a) or increased water solubility (10b). Our preliminary SAR study at C(18) suggested that this part of the molecule interacts with a tight lipophilic pocket of the K-receptor. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.093
• 作为产物：
  描述：

  SALVINORINB(品牌:CAYMAN进口) 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 对硝基苯甲酸 、 potassium carbonate 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 生成 C-2-epi-salvinorin B
  参考文献：
  名称：

  丹参中新环戊烷二萜类化合物的合成研究：鉴定一种有效的中枢作用μ阿片类镇痛剂，降低了滥用的责任

  摘要：

  阿片类药物被广泛用于治疗数百万的痛苦患者，但由于相关的副作用，其止痛作用受到限制。在这里，我们报告显示出止痛和减少的阿片类药物引起的副作用的化学探针的发展和评估。这种化合物，kurkinorin（5）是一种有效的选择性μ阿片受体（MOR）激动剂（EC 50 = 1.2 nM，选择性> 8000μ/κ）。图5是MOR诱导的G蛋白信号转导于β-arrestin-2募集的偏向活化剂。对5 '与MOR晶体结构结合的动力学研究表明，从能量学角度出发，优选的结合方式不同于晶体配体。5的体内研究证明了中枢介导的抗伤害感受，显着降低了奖励效果，耐受性和镇静作用。我们建议，这种新型的MOR激动剂可能代表从其副作用中区分参与MOR诱导的镇痛的途径的有价值的工具。

  DOI：

  10.1021/acs.jmedchem.6b01235

文献信息

• Total Synthesis of the Hallucinogenic Neoclerodane Diterpenoid Salvinorin A
  作者：Masato Nozawa、Yuhki Suka、Takashi Hoshi、Toshio Suzuki、Hisahiro Hagiwara

  DOI：10.1021/ol800101v

  日期：2008.4.1

  Total synthesis of salvinorin A (1), a neoclerodane diterpenoid having the most potent hallucinogenic activity and a selective K-opioid agonist, was completed in 20 steps starting from enantiomerically pure hydroxy-Wieland-Miescher ketone 5.
• Synthesis and in vitro evaluation of salvinorin A analogues: Effect of configuration at C(2) and substitution at C(18)
  作者：Cécile Béguin、Michele R. Richards、Jian-Guo Li、Yulin Wang、Wei Xu、Lee-Yuan Liu-Chen、William A. Carlezon、Bruce M. Cohen

  DOI：10.1016/j.bmcl.2006.05.093

  日期：2006.9

  kappa-opioid receptor ligands have raised interest for their apparent effects on mood. The potent and selective kappa-agonist salvinorin A has short-lasting (15 min) depressive-like effects in rats in behavioral models used to study mood disorders. Two series of salvinorin derivatives modified at C(2) and C(18), respectively, were synthesized and their kappa-opioid receptor affinities, potencies, and efficacies were evaluated using in vitro receptor binding and biochemical functional assays. Modification at C(2) yielded potent kappa-agonists that are predicted to have improved metabolic stability (14a, 15a) or increased water solubility (10b). Our preliminary SAR study at C(18) suggested that this part of the molecule interacts with a tight lipophilic pocket of the K-receptor. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthetic Studies of Neoclerodane Diterpenes from <i>Salvia divinorum:</i> Identification of a Potent and Centrally Acting μ Opioid Analgesic with Reduced Abuse Liability
  作者：Rachel Saylor Crowley、Andrew P. Riley、Alexander M. Sherwood、Chad E. Groer、Nirajmohan Shivaperumal、Miguel Biscaia、Kelly Paton、Sebastian Schneider、Davide Provasi、Bronwyn M. Kivell、Marta Filizola、Thomas E. Prisinzano

  DOI：10.1021/acs.jmedchem.6b01235

  日期：2016.12.22

  Opioids are widely used to treat millions suffering from pain, but their analgesic utility is limited due to associated side effects. Herein we report the development and evaluation of a chemical probe exhibiting analgesia and reduced opioid-induced side effects. This compound, kurkinorin (5), is a potent and selective μ-opioid receptor (MOR) agonist (EC50 = 1.2 nM, >8000 μ/κ selectivity). 5 is a biased

  阿片类药物被广泛用于治疗数百万的痛苦患者，但由于相关的副作用，其止痛作用受到限制。在这里，我们报告显示出止痛和减少的阿片类药物引起的副作用的化学探针的发展和评估。这种化合物，kurkinorin（5）是一种有效的选择性μ阿片受体（MOR）激动剂（EC 50 = 1.2 nM，选择性> 8000μ/κ）。图5是MOR诱导的G蛋白信号转导于β-arrestin-2募集的偏向活化剂。对5 '与MOR晶体结构结合的动力学研究表明，从能量学角度出发，优选的结合方式不同于晶体配体。5的体内研究证明了中枢介导的抗伤害感受，显着降低了奖励效果，耐受性和镇静作用。我们建议，这种新型的MOR激动剂可能代表从其副作用中区分参与MOR诱导的镇痛的途径的有价值的工具。