Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy; CNR NANOTEC, Campus Ecotekne of the University of Salento, Via Monteroni, 73100, Lecce, Italy.
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
J Pharm Biomed Anal. 2019 Oct 25;175:112752. doi: 10.1016/j.jpba.2019.06.049. Epub 2019 Jul 12.
Cannabidiol (CBD), one of the two major active principles present in Cannabis sativa, is gaining great interest among the scientific community for its pharmaceutical, nutraceutical and cosmetic applications. CBD can be prepared either by chemical synthesis or extraction from Cannabis sativa (hemp). The latter is more convenient from several points of view, including environmental and economic, but mainly for the absence of harmful organic solvents generally employed in the chemical synthesis. Although CBD produced by hemp extraction is the most widely employed, it carries two major impurities. The first one is the already known cannabidivarin (CBDV), whereas the second one is supposed to be the butyl analog of CBD with a four-term alkyl side chain. In this work, we report the isolation by semi-preparative liquid chromatography and the unambiguous identification of this second impurity. A comprehensive spectroscopic characterization, including NMR, UV, IR, circular dichroism and high-resolution mass spectrometry (HRMS), was carried out on this natural cannabinoid. In order to confirm its absolute configuration and chemical structure, the stereoisomer (1R,6R) of the supposed cannabinoid was synthesized and the physicochemical and spectroscopic properties, along with the stereochemistry, matched those of the natural isolated molecule. According to the International Nonproprietary Name, we suggested the name of cannabidibutol (CBDB) for this cannabinoid. Lastly, an HPLC-UV method was developed and validated for the qualitative and quantitative determination of CBDV and CBDB in samples of CBD extracted from hemp and produced according to Good Manufacturing Practices regulations for pharmaceutical and cosmetic use.
大麻二酚（CBD）是大麻中存在的两种主要活性成分之一，由于其在药物、营养保健品和化妆品方面的应用，正在引起科学界的极大兴趣。CBD 可以通过化学合成或从大麻（大麻）中提取来制备。从几个方面来看，包括环境和经济方面，但主要是因为化学合成中通常使用的有害有机溶剂的缺失，后者更为方便。虽然由大麻提取的 CBD 是使用最广泛的，但它携带两种主要杂质。第一种是已经知道的大麻二酚（CBDV），而第二种则被认为是 CBD 的丁基类似物，具有四元烷基侧链。在这项工作中，我们通过半制备液相色谱法分离并明确鉴定了这种第二种杂质。对这种天然大麻素进行了全面的光谱表征，包括 NMR、UV、IR、圆二色性和高分辨率质谱（HRMS）。为了确认其绝对构型和化学结构，合成了假定大麻素的立体异构体（1R，6R），并对其物理化学和光谱性质以及立体化学进行了研究，与天然分离分子的性质相匹配。根据国际非专利名称，我们建议将这种大麻素命名为大麻二丁醇（CBDB）。最后，开发并验证了一种 HPLC-UV 方法，用于定性和定量测定符合良好生产规范（GMP）规定的用于制药和化妆品用途的大麻中提取的 CBDV 和 CBDB 的含量。
