1'-hydroxy-Δ8-tetrahydrocannabinol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1'-hydroxy-Δ8-tetrahydrocannabinol
• 英文别名: (6aR,10aR)-3-(1-hydroxypentyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol
• 化学式: C₂₁H₃₀O₃
• 分子量: 330.467
• InChiKey: ZZNJYNWMTPQDJR-YNPPLXCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (-)-Δ8-四氢大麻酚 在 cytochrome P₄₅₀ reductase 、 cytochrome P₄₅₀ 2J₂ 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.5h， 生成 1'-hydroxy-Δ8-tetrahydrocannabinol
  参考文献：
  名称：

  Cross-talk of cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2

  摘要：

  Phytocannabinoids have well-known cardiovascular implications. For instance, Delta 9-tetrahydrocannabinol (Delta 9-THC), the principal component of cannabis, induces tachycardia in humans. In order to understand the impact of phytocannabinoids on human cardiovascular health, there is a need to study the metabolism of phytocannabinoids by cardiac cytochromes p450 (CYPs). CYP2J2, the primary CYP of cardiomyocytes, is responsible for the metabolism of the endocannabinoid, anandamide (AEA), into cardioprotective epoxides (EET-EAs). Herein, we have investigated the kinetics of the direct metabolism of six phytocannabinoids (Delta 9-THC, Delta 8-tetra-hydrocannabinol, cannabinol, cannabidiol, cannabigerol, and cannabichromene) by CYP2J2. CYP2J2 mainly produces 1'/1 ''-OH metabolites of these phytocannabinoids. These phytocannabinoids are metabolized with greater catalytic efficiency compared to the metabolism of AEA by CYP2J2. We have also determined that the phytocannabinoids are potent inhibitors of CYP2J2-mediated AEA metabolism, with Delta 9-THC being the strongest inhibitor. Most of the inhibition of CYP2J2 by the phytocannabinoids follow a noncompetitive inhibition model, and therefore dramatically reduce the formation of EET-EAs by CYP2J2. Taken together, these data demonstrate that phytocannabinoids are directly metabolized by CYP2J2 and inhibit human cardiac CYP2J2, leading to a reduction in the formation of cardioprotective EET-EAs.

  DOI：

  10.1016/j.jinorgbio.2018.03.016

文献信息

• Human liver microsomal oxidation of .DELTA.8-tetrahydrocannabinol.
  作者：Ikuo Yamamoto、Shizuo Narimatsu、Kazuhito Watanabe、Tatsuyuki Shimonishi、Hidetoshi Yoshimura、Taizo Nagano

  DOI：10.1248/cpb.31.1784

  日期：——

  Human Liver microsomal oxidation products of Δ8-tetrahydrocannabinol (THC) were isolated and identified by thin-layer chromatography, gas chromatography and gas chromatography-mass spectrometry. As the results, five monohydroxylated metabolites including 11-hydroxy-Δ8-THC, and 8β, 9α-dihydroxyhexahydrocannabinol were identified as trimethyl-silyl derivatives. Isolation of the dihydroxylated metabolite suggests that epoxy metabolite (s) may be formed from Δ8-THC in humans.

  通过薄层色谱法、气相色谱法和气相色谱-质谱法分离和鉴定了Δ8-四氢大麻酚（THC）的人肝微粒体氧化产物。结果发现，包括 11-hydroxy-Δ8-THC 和 8β、9α-dihydroxyhexahydrocannabinol 在内的五种单羟基代谢物被鉴定为三甲基硅烷衍生物。二羟基代谢物的分离表明，Δ8-THC 在人体中可能会形成环氧代谢物。
• Cross-talk of cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2
  作者：William R. Arnold、Austin T. Weigle、Aditi Das

  DOI：10.1016/j.jinorgbio.2018.03.016

  日期：2018.7

  Phytocannabinoids have well-known cardiovascular implications. For instance, Delta 9-tetrahydrocannabinol (Delta 9-THC), the principal component of cannabis, induces tachycardia in humans. In order to understand the impact of phytocannabinoids on human cardiovascular health, there is a need to study the metabolism of phytocannabinoids by cardiac cytochromes p450 (CYPs). CYP2J2, the primary CYP of cardiomyocytes, is responsible for the metabolism of the endocannabinoid, anandamide (AEA), into cardioprotective epoxides (EET-EAs). Herein, we have investigated the kinetics of the direct metabolism of six phytocannabinoids (Delta 9-THC, Delta 8-tetra-hydrocannabinol, cannabinol, cannabidiol, cannabigerol, and cannabichromene) by CYP2J2. CYP2J2 mainly produces 1'/1 ''-OH metabolites of these phytocannabinoids. These phytocannabinoids are metabolized with greater catalytic efficiency compared to the metabolism of AEA by CYP2J2. We have also determined that the phytocannabinoids are potent inhibitors of CYP2J2-mediated AEA metabolism, with Delta 9-THC being the strongest inhibitor. Most of the inhibition of CYP2J2 by the phytocannabinoids follow a noncompetitive inhibition model, and therefore dramatically reduce the formation of EET-EAs by CYP2J2. Taken together, these data demonstrate that phytocannabinoids are directly metabolized by CYP2J2 and inhibit human cardiac CYP2J2, leading to a reduction in the formation of cardioprotective EET-EAs.