Antiarrhythmic agents based on diterpenoid alkaloid lappaconitine. Protonation of N-deacethyllappaconitine in methanol solutions

• Published in: Russian chemical bulletin Vol. 69; no. 3; pp. 567 - 571
• Main Authors: Akhiyarov, A. A., Lobov, A. N., Ivanov, S. P., Spirikhin, L. V., Gabbasov, T. M., Tsyrlina, E. M., Valiev, N. V., Sadikov, A. Z., Sagdullaev, Sh. Sh, Yunusov, M. S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2020; Springer Nature B.V
• Subjects: Basicity; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Full Articles; Hydrobromides; Hydrochlorides; Inorganic Chemistry; Metabolites; Nitrogen atoms; NMR spectroscopy; Organic Chemistry; Protonation; Titration; lappaconitine; diterpene alkaloids; salt formation; stepwise protonation; antiarrhythmics; deacetyllappaconitine; drug
• ISSN: 1066-5285; 1573-9171
• DOI: 10.1007/s11172-020-2800-0

The data on antiarrhythmic drugs based on diterpene alkaloid lappaconitine are summarized. N -Deacetyllappaconitine is the main metabolite of allapinin and a potential antiarrhythmics for intravenous use. The basicity of two nitrogen atoms of this compound and the possibility of obtaining mono- and di-salts with the example of hydrochlorides and hydrobromides having good solubility in water have been studied. It was shown using NMR spectroscopy and potentiometric titration that in the methanolic solutions the atom N(20) is protonated at the first step (p K b1 = 6.77, 25 °C) in the pH range of 6—7. The nitrogen of the primary aromatic amino group is protonated in the pH range of 2—3 (p K b2 = 2.18, 25 °C).