(5aS,6S,9R,9aR)-5a,6,7,8,9,9a-六氢-6-甲基-9-(1-甲基乙烯基)-3-戊基-1,6-二苯并呋喃二醇 | 52025-76-0

• 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
• 中文名称: (5aS,6S,9R,9aR)-5a,6,7,8,9,9a-六氢-6-甲基-9-(1-甲基乙烯基)-3-戊基-1,6-二苯并呋喃二醇
• 英文名称: cannabielsoin A
• 英文别名: cannnabielsoin；cannabielsoin；CBE；(5aS,6S,9R,9aR)-6-methyl-3-pentyl-9-prop-1-en-2-yl-7,8,9,9a-tetrahydro-5aH-dibenzofuran-1,6-diol
• CAS: 52025-76-0
• 化学式: C₂₁H₃₀O₃
• 分子量: 330.467
• InChiKey: RBEAVAMWZAJWOI-MTOHEIAKSA-N

物化性质

• 沸点：
  426.5±45.0 °C(Predicted)
• 密度：
  1.089±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：50mg/mL； DMSO：60mg/mL； DMSO:PBS (pH 7.2) (1:3)：0.25 mg；乙醇：35mg/mL
• 保留指数：
  2435

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  5
• 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

ADMET

代谢

在现有文献中没有找到关于二苯并呋喃在哺乳动物体内的代谢信息。细菌Sphingomonas、Brevibacterium、Terrabacter和Staphylococcus auricularis通过二苯并呋喃4,4a-二加氧酶将二苯并呋喃降解为2,2',3-三羟基联苯。

No information on the metabolism of dibenzofuran in mammalian organisms was found in the available literature. The bacteria Sphingomonas, Brevibacterium, Terrabacter, and Staphylococcus auricularis degrade dibenzofuran to 2,2',3-trihydroxybiphenyl via dibenzofuran 4,4a-dioxygenase. (L952)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

二苯并呋喃能结合芳烃受体，这增加了它激活XRE启动子区域转录的能力。这改变了许多基因的表达。（A586）

Dibenzofurans bind the aryl hydrocarbon receptor, which increases its ability to activate transcription in the XRE promoter region. This alters the expression of a number of genes. (A586)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

无致癌性迹象（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity (not listed by IARC). (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

CDFs会导致呕吐和腹泻、贫血、更频繁的肺部感染、麻木以及神经系统等其他影响，以及肝脏的轻微变化。然而，在摄入CDFs的人中没有发现永久性的肝脏变化或明确的肝脏损伤。

CDFs cause vomiting and diarrhea, anemia, more frequent lung infections, numbness and other effects on the nervous system, and mild changes in the liver. However, there were no permanent liver changes or definite liver damage found in people who ingested CDFs. (L952)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

吸入 (L952) ; 皮肤 (L952) ; 口服 (L952)

Inhalation (L952) ; dermal (L952) ; oral (L952)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

皮肤和眼部刺激，尤其是严重的痤疮、肤色变黑和带有分泌物的肿胀眼睑是CDF中毒最明显的健康影响。

Skin and eye irritations, especially severe acne, darkened skin color, and swollen eyelids with discharge are the most obvious health effects of the CDF poisoning. (L952)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  (5aS,6S,9R,9aR)-5a,6,7,8,9,9a-六氢-6-甲基-9-(1-甲基乙烯基)-3-戊基-1,6-二苯并呋喃二醇 在 4-二甲氨基吡啶 、 氯化亚砜 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 16.03h， 生成 6-methyl-3-pentyl-9-(prop-1-en-2-yl)dibenzo[b,d]furan-1-yl acetate
  参考文献：
  名称：

  Synthesis of the Cannabimovone and Cannabifuran Class of Minor Phytocannabinoids and Their Anti-inflammatory Activity

  摘要：

  DOI：

  10.1021/acs.joc.2c00336
• 作为产物：
  描述：

  大麻二酚 在 ethylene diamine tetraacetic acid tetrasodium salt 、 sodium carbonate 、 oxone(R) 作用下， 以 丙酮 为溶剂， 以60 %的产率得到(5aS,6S,9R,9aR)-5a,6,7,8,9,9a-六氢-6-甲基-9-(1-甲基乙烯基)-3-戊基-1,6-二苯并呋喃二醇
  参考文献：
  名称：

  从 CBD 轻松便捷地合成大麻素

  摘要：

  大麻二酚（CBD）是在各种大麻化学型中发现的一种重要的植物大麻素，其治疗潜力正在接受广泛的研究。此外，由于它不具有精神活性，因此在某些国家，根据其法律地位，它也可以用作食品和补充剂中的功能成分。从化学反应性的角度来看，CBD 在储存期间和消费基于 CBD 的产品后都可以转化为不同结构相关的化合物。由于潜在的毒性和失去活性成分 (CBD) 所有权的风险，这些化合物的分析测定至关重要。因此，代表性 CBD 衍生化合物的完全立体选择性全合成已成为人们极大的兴趣。通过几个合成步骤即可合成纯 CBD 衍生化合物，这对于准备分析标准品和促进生物学研究至关重要。本文详细介绍了将现成的 CBD 转化为 Δ 8 -THC、Δ 9 -THC、Δ 8 - iso -THC、CBE、HCDN、CBDQ、Δ 6 - iso -CBD 和 1,8-cineol 大麻素 (CCB) ）。所描述的方案的执行没有广泛使用保

  DOI：

  10.1021/acs.jnatprod.3c01117

文献信息

• In vivo and in vitro metabolism of cannabidiol monomethyl ether and cannabidiol dimethyl ether in the guinea pig: On the formation mechanism of cannabielsoin-type metabolite from cannabidiol.
  作者：Hiroshi GOHDA、Shizuo NARIMATSU、Ikuo YAMAMOTO、Hidetoshi YOSHIMURA

  DOI：10.1248/cpb.38.1697

  日期：——

  Oxidative metabolism of cannabidiol monomethyl ether (CBDM), one of the components of marihuana, was studied in the guinea pig. Cannabielsoin monomethyl ether (CBEM) was found to be formed with hepatic microsomes by gas chromatography-mass spectrometry (GC-MS). Experiments using various modifiers of enzymatic reaction suggested that, as in the case of cannabielsoin (CBE) formation from canabidiol (CBD), CBEM was formed from CBDM by the monooxygenase system including cytochrome P450. When cannabidiol dimethyl ether (CBDD), in which phenolic hydroxyl groups of CBD are masked with methyl groups, was incubated with liver microsomes and an reduced nicotinamide adenine dinucleotide phosphate-generating system, 1S, 2R-epoxy-CBDD was identified by GC-MS. The epoxy metabolite was also found in the liver of a guinea pig pretreated with CBDD (100mg/kg, intraperitoneally) 1h before sacrifice. Rate of 1S, 2R-epoxide metabolism was slower than that of 1R, 2S-epoxy-CBDD under the conditions, as in the microsomal oxidation of CBDD described above. These results indicate that 1S, 2R-epoxides are formed from CBD, CBDM and CBDD and that the epoxides are quickly converted to elsoin-type metabolites in the cases of CBD and CBDM.

  研究了大麻成分之一的CBD单甲醚（CBDM）在豚鼠中的氧化代谢。通过气相色谱-质谱联用技术（GC-MS），发现通过肝微粒体形成了大麻醇单甲醚（CBEM）。使用各种酶促反应调节剂的实验表明，CBEM的形成与大麻二酚（CBD）转变为大麻醇（CBE）类似，是通过包括细胞色素P450在内的单氧合酶系统从CBDM生成的。当掩盖了CBD酚羟基的甲基化合物CBD二甲醚（CBDD）与肝微粒体及还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）生成系统共同孵育时，通过GC-MS鉴定出1S, 2R-氧化CBDD。该氧化代谢物也在接受CBDD（100mg/kg，腹腔注射）预处理1小时后被处死的豚鼠肝脏中被发现。在上述条件下，1S, 2R-氧化物的代谢速率低于1R, 2S-氧化CBDD。这些结果表明，1S, 2R-氧化物是从CBD、CBDM和CBDD生成的，并且在CBD和CBDM的情况下，这些氧化物迅速转化为大麻醇类代谢物。
• Structural revision of a Wnt/β-catenin modulator and confirmation of cannabielsoin constitution and configuration
  作者：Angelina Z. Monroe、William H. Gordon、Jared S. Wood、Gary E. Martin、Jeremy B. Morgan、R. Thomas Williamson

  DOI：10.1039/d1cc01971f

  日期：——

  In this report, we revise the structure for a previously reported synthetic product proposed to be the 1R,2S-cannabidiol epoxide and reassign it as cannabielsoin using anisotropic NMR and synthetic chemistry methods. These results provide a direct link to the first known biological target and function of cannabielsoin.

  在本报告中，我们修改了先前报道的合成产品的结构，建议为 1 R ,2 S -大麻二酚环氧化物，并使用各向异性 NMR 和合成化学方法将其重新指定为大麻油。这些结果提供了与大麻素的第一个已知生物学目标和功能的直接联系。
• POLYCANNABINOIDS, COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：University of Connecticut

  公开号：US20210322365A1

  公开（公告）日：2021-10-21

  Polymers comprising a plurality of cannabinoids, methods of preparation thereof, and methods of use to treat a number of disease conditions are reported. Also provided are polymer coatings, films, fibers, and non-woven fabrics for a variety of topical applications including stents, bandages, sutures, and transdermal patches.

  本文报告了包含多种大麻素的聚合物，其制备方法以及用于治疗多种疾病状况的方法。同时，还提供了用于各种局部应用的聚合物涂层、膜、纤维和无纺布，包括支架、绷带、缝合线和经皮贴片。
• Cannabinoid composition and products including α-tocopherol
  申请人：Constance Therapeutics, Inc.

  公开号：US10238745B2

  公开（公告）日：2019-03-26

  A cannabinoid composition having an excipient including α-tocopherol and at least one isolated cannabinoid having a purity of greater than 80%. The α-tocopherol inhibits oxidation, regulates viscosity of the composition, and improves bioavailability of the cannabinoid. The composition includes a carrier oil mixed with the excipient and cannabinoid. In one embodiment, the at least one cannabinoid is an isolated cannabinoid having a greater than 80% purity, and preferably greater than 90% purity. The at least one cannabinoid is selected from the group consisting of phytocannabinoids, endocannabinoids, synthetic cannabinoids, and combinations thereof. The cannabinoid may be derived from plants other than cannabis sativa, or synthesized from fungi, bacteria, yeast or other synthetic method. Preferably the α-tocopherol comprises at least 10% w/w of the composition.

  一种大麻素组合物，其赋形剂包括α-生育酚和至少一种纯度大于 80% 的分离大麻素。α-生育酚可抑制氧化，调节组合物的粘度，提高大麻素的生物利用度。组合物包括与赋形剂和大麻素混合的载体油。在一个实施方案中，至少一种大麻素是分离出来的大麻素，纯度大于 80%，最好大于 90%。至少一种大麻素选自植物大麻素、内源性大麻素、合成大麻素及其组合组成的组。大麻素可以从大麻以外的植物中提取，也可以从真菌、细菌、酵母或其他合成方法中合成。α-生育酚最好至少占组合物重量的 10%。
• Cannabis oil extracts and compositions
  申请人：CONSTANCE THERAPEUTICS, INC.

  公开号：US10406186B2

  公开（公告）日：2019-09-10

  The present invention provides cannabis oil extracts and compositions thereof, including cannabis oil compositions containing vitamin E, and methods for preparing the extracts and compositions. In some embodiments, the present invention provides a method for preparing a cannabis oil extract comprising eluting cannabinoids from cannabis plant material with a solvent to produce an eluate, filtering the eluate with a filter to produce a filtrate, evaporating the solvent from the filtrate with a distiller to produce a distillate, and purging the distillate under conditions sufficient to remove residual solvent, thereby preparing the extract. In some embodiments, the method further includes mixing a quantity of vitamin E with the extract to produce a cannabis oil composition.

  本发明提供了大麻油提取物及其组合物，包括含有维生素 E 的大麻油组合物，以及制备提取物和组合物的方法。在一些实施方案中，本发明提供了一种制备大麻油提取物的方法，包括用溶剂从大麻植物材料中洗脱大麻素以产生洗脱液，用过滤器过滤洗脱液以产生滤液，用蒸馏器蒸发滤液中的溶剂以产生蒸馏物，在足以除去残留溶剂的条件下净化蒸馏物，从而制备提取物。在某些实施方案中，该方法还包括将一定量的维生素 E 与萃取物混合，制成大麻油组合物。