(2S,4aR,6aR,7R,10aS,10bR)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester | 876169-08-3

• 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: (2S,4aR,6aR,7R,10aS,10bR)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester
• 英文别名: methyl (2S,4aR,6aR,7R,10aS,10bR)-2-(Furan-3-yl)-6a,10b-dimethyl-4,10-dioxododecahydro-2H-benzo[f ]isochromene-7-carboxylate；methyl (1R,6R,7R,8R,10R,13S)-13-(3-furyl)-1,7-dimethyl-3,11-dioxo-12-oxatricyclo-[8.4.0.0(2,7)]tetradecane-6-carboxylate；methyl (13S,1R,6R,7R)-13-(3-furyl)-1,7-dimethyl-12-oxa-3,11-dioxotricyclo[8.4.0.0(2,7)]tetradecane-6-carboxylate；2-deacetoxysalvinorin A；desacetoxy salvinorin A；(2S,4aR,6aR,7R,9S,10aS,10bR)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]-pyran-7-carboxylic acid methyl ester；methyl (2S,4aR,6aR,7R,10aS,10bR)-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: 876169-08-3
• 化学式: C₂₁H₂₆O₆
• 分子量: 374.434
• InChiKey: DWBSPRNBPGOZCH-KDBJUTIMSA-N

物化性质

• 熔点：
  149 °C
• 沸点：
  521.4±50.0 °C(predicted)
• 密度：
  1.213±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 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：
  82.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4aR,6aR,7R,10aS,10bR)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester 、 三乙基氯硅烷 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 0.52h， 以100%的产率得到methyl (2S,7R,10bR,4aR,6ar)-2-(3-furyl)-10b,6a-dimethyl-4-oxo-10-(triethylsilanyloxy)-5,6,7,8,10a,10b,4a,6a-octahydrobenzo[3,2-f]isochromane-7-carboxylate
  参考文献：
  名称：

  Total Synthesis of the Hallucinogenic Neoclerodane Diterpenoid Salvinorin A

  摘要：

  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.

  DOI：

  10.1021/ol800101v
• 作为产物：
  描述：

  SALVINORINB(品牌:CAYMAN进口) 在 4-二甲氨基吡啶 、 过氧化双月桂酰 、 二苯基硅烷 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 0.75h， 生成 (2S,4aR,6aR,7R,10aS,10bR)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester
  参考文献：
  名称：

  Addressing Structural Flexibility at the A-Ring on Salvinorin A: Discovery of a Potent Kappa-Opioid Agonist with Enhanced Metabolic Stability

  摘要：

  Previous structure-activity studies on the neoclerodane diterpenoid salvinorin A have demonstrated the importance of the acetoxy functionality on the A-ring in its activity as a kappa-opioid receptor agonist. Few studies have focused on understanding the role of conformation in these interactions. Herein we describe the synthesis and evaluation of both flexible and conformationally restricted compounds derived from salvinorin A. One such compound, spirobutyrolactone 14, was synthesized in a single step from salvinorin B and had similar potency and selectivity to salvinorin A (EC50 = 0.6 +/- 0.2 nM at kappa; >10000 nM at mu and delta). Microsomal stability studies demonstrated that 14 was more metabolically resistant than salvinorin A. Evaluation of analgesic and anti-inflammatory properties revealed similar in vivo effects between 14 and salvinorin A. To our knowledge, this study represents the first example of bioisosteric replacement of an acetate group by a spirobutyrolactone to produce a metabolically resistant derivative.

  DOI：

  10.1021/acs.jmedchem.7b00148

文献信息

• Opioid receptor ligands and methods for their preparation
  申请人：Prisinzano Thomas

  公开号：US20060058264A1

  公开（公告）日：2006-03-16

  The invention provides novel compounds of formula I: that are opioid receptor ligands. The invention also provides pharmaceutical compositions comprising such compounds as well as methods for treating diseases associated with opioid receptor function by administering such compounds to a mammal in need of treatment. The invention also provides an improved method for isolating intermediate materials useful for obtaining compounds of formula I.

  该发明提供了公式I的新化合物，这些化合物是阿片受体配体。该发明还提供了包含这些化合物的药物组合物，以及通过向需要治疗的哺乳动物施用这些化合物来治疗与阿片受体功能相关的疾病的方法。该发明还提供了一种改进的方法，用于分离中间体材料，以获得公式I的化合物。
• Synthetic Studies of Neoclerodane Diterpenes from <i>Salvia </i><i>d</i><i>ivinorum</i>:  Semisynthesis of Salvinicins A and B and Other Chemical Transformations of Salvinorin A
  作者：Wayne W. Harding、Matthew Schmidt、Kevin Tidgewell、Pavitra Kannan、Kenneth G. Holden、Brian Gilmour、Hernan Navarro、Richard B. Rothman、Thomas E. Prisinzano

  DOI：10.1021/np050398i

  日期：2006.1.1

  Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the widely available psychoactive plant Salvia divinorum and is the first example of a non-nitrogenous opioid receptor ligand. At present, there is little information available as to why this compound is selective for kappa opioid receptors. One approach to better understanding the mode of binding of 1 at kappa receptors is to

  Salvinorin A（1）是从广泛使用的精神活性植物Salvia divinorum中分离出的致幻新环戊二烯二萜，是非氮类阿片受体配体的第一个实例。目前，关于这种化合物为什么对κ阿片受体具有选择性的信息很少。更好地了解1在kappa受体上的结合方式的一种方法是系统地改变1的结构并检查对阿片受体亲和力和活性的影响。当前，描述用于制备源自1的类似物的方法很少。这里，我们报道了对从S. divinorum分离的1的几种化学转化的研究。特别是，
• 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。
• Second-generation synthesis of salvinorin A
  作者：Hisahiro Hagiwara、Yuhki Suka、Takashi Nojima、Takashi Hoshi、Toshio Suzuki

  DOI：10.1016/j.tet.2009.04.053

  日期：2009.6

  Functionalization toward total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A was accomplished via three double sequences: bis-enol triflate synthesis, palladium-catalyzed double carbonylation to the bis-enol triflate, and samarium diiodide-mediated double conjugate reduction. The configuration at C-12 was controlled by chelation-controlled diastereoselective reduction.

  通过三个双序列实现了产生致幻剂的新环戊烷二萜类沙尔维诺林A的功能化：双烯醇三氟甲磺酸酯的合成，钯催化的双羰基化为双烯醇的三氟甲磺酸酯和sa碘化ide介导的双共轭物的还原。通过螯合控制的非对映选择性还原来控制C-12处的构型。
• Formal Synthesis of (±)‐Salvinorin A via Gold(I) Catalysis
  作者：Huy Tran、Philippe McGee、Louis Barriault

  DOI：10.1002/chem.202301640

  日期：2023.9

  A formal synthesis of (±)-Salvinorin A, a neo clerodane diterpenoid natural product and μ-opioid receptor agonist, is being reported utilizing a double application of gold(I) methodology as a Lewis acid and a photoredox catalyst.

  据报道，利用金（I）方法作为路易斯酸和光氧化还原催化剂的双重应用，正式合成了（±）-Salvinorin A，一种新氯烷二萜天然产物和μ-阿片受体激动剂。