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Updated: May 22, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and Structural Analysis of New (-)-Cytisine Squaramides
Anna K Przybył1, Jan Janczak2, Adam Huczyński1
1Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.
Abstract:
Derivatives of squaric acid are valuable building blocks with promising applications in the investigation of various bioactivities. In this study, we focus on squaramides functionalized with the (-)-cytisine moiety, an alkaloid known for its bioactivity as a nicotinic acetylcholine receptor agonist and its application in nicotine addiction treatment. Reactions of cytisine-monosquarate with several amines, such as ammonia, propargylamine, and morpholine, led to the formation of novel conjugates of cytisine-squaramides. Additionally, squaramide containing two cytisine moieties was synthesized via the reaction of diethyl squarate with cytisine at a 1:2 molar ratio. All obtained squaramides were thoroughly characterized by MS, FT-IR, and NMR methods and by single-crystal X-ray diffraction analysis. To gain deeper insights into their structural properties and intermolecular interactions, geometry optimizations were performed using DFT calculations, complemented with 3D molecular electrostatic potential maps.
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