(1R,4R,5R)-4-[4-(7-bromo-2-methylheptan-2-yl)-2,6-dihydroxyphenyl]-6,6-dimethylbicyclo[3.1.1]heptan-2-one | 941583-48-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,4R,5R)-4-[4-(7-bromo-2-methylheptan-2-yl)-2,6-dihydroxyphenyl]-6,6-dimethylbicyclo[3.1.1]heptan-2-one
• CAS: 941583-48-8
• 化学式: C₂₃H₃₃BrO₃
• 分子量: 437.417
• InChiKey: PRWLSIGBFXQYDL-ZACQAIPSSA-N

反应信息

• 作为反应物：
  描述：

  (1R,4R,5R)-4-[4-(7-bromo-2-methylheptan-2-yl)-2,6-dihydroxyphenyl]-6,6-dimethylbicyclo[3.1.1]heptan-2-one 在 咪唑 、 4-二甲氨基吡啶 、 三氟甲磺酸三甲基硅酯 、 双(三甲基硅烷基)氨基钾 、 三氯乙酸 作用下， 以 四氢呋喃 、 硝基甲烷 、 二氯甲烷 为溶剂， 反应 17.91h， 生成 (6aR,10aR)-3-(7-bromo-2-methylheptan-2-yl)-1-[(tert-butyldimethylsilyl)oxy]-6,6-dimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene-9-carbaldehyde
  参考文献：
  名称：

  Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex Structures

  摘要：

  Human endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hindered the development of therapeutic applications. Importantly, missing structural information has significantly held back the development of promising CB2-selective agonist drugs for treating inflammatory and neuropathic pain without the psychoactivity of CB1. Here, we report the cryoelectron microscopy structures of synthetic cannabinoid-bound CB2 and CB1 in complex with G(i), as well as agonist-bound CB2 crystal structure. Of important scientific and therapeutic benefit, our results reveal a diverse activation and signaling mechanism, the structural basis of CB2-selective agonists design, and the unexpected interaction of cholesterol with CB1, suggestive of its endogenous allosteric modulating role.

  DOI：

  10.1016/j.cell.2020.01.008