Diastereoselective Synthesis and Biological Evaluation of Spiro[chromane-2,4′-pyrimidin]-2′(3′H)-ones as Novel Antimicrobial and Antioxidant Agents

Karandeeva A.S. Bogdanova N.A. Kabanova M.V. Filimonov S.I. Chirkova Z.V. Romanycheva A.A. Panova V.A. Shetnev A.A. Togyzbayeva N.A. Kanzhar S.A. Appazov N.O. Suponitsky K.Y.
July 2025 Multidisciplinary Digital Publishing Institute (MDPI)

Molecules
2025 #30 Issue 14

This study reports an improved diastereoselective synthesis of substituted spiro[chromane-2,4′-pyrimidin]-2′(3′H)-ones via the acid-catalyzed condensation of 6-styryl-4-aryldihydropyrimidin-2-ones with resorcinol, 2-methylresorcinol, and pyrogallol. The optimized method allows for the isolation of diastereomerically pure products, with stereoselectivity controlled by varying acid catalysts (e.g., methanesulfonic acid vs. toluenesulfonic acid) and solvent conditions. The synthesized compounds were evaluated for antimicrobial and antioxidant activities. Notably, the (2S*,4R*,6′R*)-diastereomers exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains with minimal inhibition concentration down to 2 µg/mL, while derivatives containing vicinal bisphenol moieties demonstrated potent antioxidant activity, with IC₅₀ values (12.5 µg/mL) comparable to ascorbic acid. Pharmacokinetic analysis of selected hit compounds revealed favorable drug-like properties, including high gastrointestinal absorption and blood-brain barrier permeability. These findings highlight the potential of spirochromane-pyrimidine hybrids as promising candidates for further development in the treatment of infectious diseases and oxidative stress-related pathologies.

2-methylresorcinol , acid catalysis , antimicrobial activity , antioxidant activity , diastereoselective synthesis , heterocycles , pharmacokinetics , pyrogallol , resorcinol , spirochromane-pyrimidines

Text of the article Перейти на текст статьи

Institute of Chemistry and Chemical Technology, Yaroslavl State Technical University, Moskovskii Prosp. 88, Yaroslavl, 150023, Russian Federation
Pharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named After K.D. Ushinsky, Respublikanskaya Str. 108, Yaroslavl, 150000, Russian Federation
Moscow Center for Advanced Studies, Kulakova Str. 20, Moscow, 123592, Russian Federation
Laboratory of Engineering Profile, Korkyt Ata Kyzylorda University, Aiteke Bi Str., Kyzylorda, 29A, 120014, Kazakhstan
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Build. 1, Vavilova Str. 28, Moscow, 119991, Russian Federation

Institute of Chemistry and Chemical Technology
Pharmaceutical Technology Transfer Centre
Moscow Center for Advanced Studies
Laboratory of Engineering Profile
A. N. Nesmeyanov Institute of Organoelement Compounds

10 лет помогаем публиковать статьи Международный издатель

Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026