O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization
Kateryna V Dil1,2, Vitalii A Palchykov1
1Research Institute of Chemistry and Geology, Oles Honchar Dnipro National University, Nauky Av. 72, Dnipro, 49045, Ukraine.
Beilstein Journal of Organic Chemistry
|September 3, 2024
Summary
A novel Biginelli synthesis efficiently produces dihydropyrimidinones (DHPMs) using a β-ketosulfone. This method yields diverse compounds, including a potential anticancer drug analog, with promising biological activities.
Area of Science:
- Organic Synthesis
- Medicinal Chemistry
- Catalysis
Background:
- The Biginelli reaction is a cornerstone for synthesizing dihydropyrimidinones (DHPMs).
- Developing efficient and versatile synthetic routes for DHPMs is crucial for drug discovery.
- Exploring novel catalysts and reaction conditions can enhance yield and selectivity.
Purpose of the Study:
- To develop a one-pot, three-component Biginelli synthesis for dihydropyrimidinones/thiones/selenones.
- To investigate the utility of Ytterbium triflate [Yb(OTf)3] as a catalyst for this tandem reaction.
- To synthesize and evaluate novel DHPM derivatives, including an SO2-containing analog of enastron.
Main Methods:
- One-pot, three-component Biginelli reaction utilizing β-ketosulfone (dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide), urea, and arylaldehyde.
- Catalysis using acetic acid or solvent-free Yb(OTf)3.
- Gram-scale synthesis and subsequent derivatization of Biginelli products into condensed thiazoles and tetrazoles.
- In silico assessment of ADMET parameters.
Main Results:
- High chemo- and regioselectivity achieved in the Biginelli synthesis.
- Diverse DHPMs synthesized in reasonable yields up to 95%.
- Successful gram-scale synthesis of an SO2-containing analog of enastron.
- Demonstrated reactivity of Biginelli products for synthesizing condensed thiazoles and tetrazoles.
- In silico ADMET analysis indicated lead-likeness for most compounds.
Conclusions:
- The developed Biginelli synthesis offers an efficient route to diverse DHPMs and their derivatives.
- The method is suitable for gram-scale synthesis of potential drug candidates.
- Synthesized compounds exhibit promising biological activity against various pathogens and diseases, including Candida albicans and Leishmania amazonensis.
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