Trotsko Nazar, Miroslaw Barbara, Jasiński Radomir, Długosz Mateusz, Sadczuk Małgorzata, Demchuk Oleg M
Department of Organic Chemistry, Medical University of Lublin, Witolda Chodźki 4A, 20-093 Lublin, Poland.
Department of General and Coordination Chemistry and Crystallography, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University in Lublin, Marii Skłodowskiej-Curie, 2, 20-031 Lublin, Poland.
Molecules. 2024 Dec 4;29(23):5731. doi: 10.3390/molecules29235731.
Improved methods for the synthesis of nicotine are of great importance due to the wide range of applications of synthetic nicotine, which is free from contamination with nitrosamines. Herein, we present a four-step chemical synthesis of ()-nicotine, involving the reduction in myosmine, enantiomeric separation of nornicotine, and subsequent methylation of the appropriate enantiomer of nornicotine obtained. The reduction in myosmine was investigated using both electrochemical and chemical approaches, achieving up to 90% yields of pure nornicotine. To achieve the enantioseparation of nornicotine, its diastereomeric salts with chiral acids, specifically, -lauroyl-()-alanine, were obtained in a mixture of methyl -butyl ether (MTBE) and chloroform, which led to the isolation of ()-nornicotine with 92% . The structures of the obtained salts were determined by the X-ray diffraction (XRD) technique, which helped to explain the origin of enantiodiscrimination during the crystallization. The described methodology allows efficient regeneration of the reagents and solvents used, leading to cost-effective production of ()-nicotine suitable for industrial-scale applications.
由于合成尼古丁具有广泛的应用，且不含亚硝胺污染，因此改进其合成方法具有重要意义。在此，我们展示了一种合成（）-尼古丁的四步化学合成方法，包括去甲烟碱的还原、降烟碱的对映体拆分，以及所得降烟碱适当对映体的后续甲基化。使用电化学和化学方法研究了去甲烟碱的还原，纯降烟碱的产率高达90%。为了实现降烟碱的对映体拆分，在甲基叔丁基醚（MTBE）和氯仿的混合物中获得了其与手性酸（具体为-L-月桂酰-（）-丙氨酸）的非对映体盐，从而分离出了92%的（）-降烟碱。通过X射线衍射（XRD）技术确定了所得盐的结构，这有助于解释结晶过程中对映体识别的起源。所描述的方法能够有效地再生所用的试剂和溶剂，从而实现适合工业规模应用的（）-尼古丁的经济高效生产。
