Cannabitwinol, a Dimeric Phytocannabinoid from Hemp, Cannabis sativa L., Is a Selective Thermo-TRP Modulator.,Journal of Natural Products

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Cannabitwinol, a Dimeric Phytocannabinoid from Hemp, Cannabis sativa L., Is a Selective Thermo-TRP Modulator.
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-09-03 , DOI: 10.1021/acs.jnatprod.0c00668
Giuseppina Chianese ₁ , Annalisa Lopatriello ₁ , Aniello Schiano-Moriello _{2,

3} , Diego Caprioglio ₄ , Daiana Mattoteia ₄ , Emanuele Benetti ₅ , Daniele Ciceri ₅ , Lolita Arnoldi ₅ , Eric De Combarieu ₅ , Rosa M Vitale ₆ , Pietro Amodeo ₆ , Giovanni Appendino ₄ , Luciano De Petrocellis ₂ , Orazio Taglialatela-Scafati ₁

Affiliation

Cannabitwinol (CBDD, 3), the second member of a new class of dimeric phytocannabinoids in which two units are connected by a methylene bridge, was isolated from a hemp (Cannabis sativa L.) industrial extract. The structural characterization of cannabitwinol, complicated by broadening of ¹H NMR signals and lack of expected 2D NMR correlations at room temperature, was fully carried out in methanol-d₄ at −30 °C. All the attempts to prepare CBDD by reaction of CBD with formaldehyde or its iminium analogue (Eschenmoser salt) failed, suggesting that this sterically congested dimer is the result of enzymatic reactions on the corresponding monomeric acids. Analysis of the cannabitwinol profile of transient receptor potential (TRP) modulation evidenced the impact of dimerization, revealing a selectivity for channels activated by a decrease of temperature (TRPM8 and TRPA1) and the lack of significant affinity for those activated by an increase of temperature (e.g., TRPV1). The putative binding modes of cannabitwinol with TRPA1 and TRPM8 were investigated in detail by a molecular docking study using the homology models of both channels.

中文翻译：

Cannabitwinol 是一种来自 Hemp, Cannabis sativa L. 的二聚植物大麻素，是一种选择性 Thermo-TRP 调节剂。

Cannabitwinol (CBDD, 3 ) 是一类新的二聚植物大麻素的第二个成员，其中两个单元通过亚甲基桥连接，是从大麻 ( Cannabis sativa L.) 工业提取物中分离出来的。大麻二酚的结构表征因¹ H NMR 信号变宽和室温下缺乏预期的 2D NMR 相关性而变得复杂，在甲醇-d _{4 中}完全进行在-30°C。通过 CBD 与甲醛或其亚胺类似物（Eschenmoser 盐）反应制备 CBDD 的所有尝试都失败了，这表明这种空间拥挤的二聚体是对相应单体酸进行酶促反应的结果。对瞬时受体电位 (TRP) 调节的大麻二酚谱的分析证明了二聚化的影响，揭示了对温度降低激活的通道（TRPM8 和 TRPA1）的选择性以及对温度升高激活的通道缺乏显着亲和力。例如，TRPV1）。通过使用两个通道的同源模型的分子对接研究，详细研究了大麻二酚与 TRPA1 和 TRPM8 的假定结合模式。

更新日期：2020-09-25

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