Synthesis of new biologically active compounds based on α - santonin
UDC 547.91:577.1:661.7
Abstract
3-Keto-6,11β,7α(H)-eudesm-1(2),4(5)-dien-6,12-olide is a sesquiterpene γ-lactone of the eudesmane structural type, known as α-santonin, isolated from more than 20 species of the genus Artemisia L. and is a renewable chemical material for the synthesis of new biologically active compounds.
The goal of the work is the synthesis of new compounds based on α-santonin with potential biological activity for the development of medicinal substances.
Methods. Hydrogenation, halogenation, oximation, aminolysis, Michael, and O-alkyl- and alkenyl-substituted oxime santonin derivatives were synthesised on the basis of the polyfunctional molecule 3-keto-6,11β,7α(H)-eudesm-1(2),4(5)-diene-6,12-olide. The antimicrobial and fungicidal activities of the samples of compounds were studied on 16 bacterial and fungal strains. Antitumour activity of the samples of compounds was studied on white mongrel rats on 6 transplantable tumour strains.
Results. 21 new compounds were synthesized, the structure of which was established on the basis of physicochemical constants, spectral data (IR, UV, 1H-, 13C NMR spectroscopy), as well as X-ray diffraction analysis. The antimicrobial, fungicidal and antitumor activities of α-santonin and its derivatives have been studied. Promising compounds for the development of new medicinal substances have been identified.
Conclusion. The reactions of regioselective nucleophilic additions of amines and alcohols to the eudesmanolide α-santonin were studied for the first time. Methods for the targeted synthesis of new hydrochloride and acetate salts of santoninamine have been developed. The relationship between the structure of the synthesized molecules and their biological activity was revealed. The results of molecular docking of the new synthesized compounds indicate their interaction with biological targets: DNA topoisomerases -I and -II, as well as SARS-CoV-2.
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