Synthesis and antimicrobial activity of functionally substituted 1,3-dioxacycloalkanes

One of the directions in the development of organic chemistry is the synthesis of biologically active compounds, including those with bactericidal activity, based on available petrochemical raw materials. In order to expand the library of bioactive compounds containing a 1,3-dioxacyclane fragment, the synthesis of derivatives of 5-acyl-5-isopropyl-1,3-dioxane – 1-(5-isopropyl-1,3-dioxane-5-yl)ethanol and (5-isopropyl-1,3-dioxane-5-yl)ethyl phenyl carbamate was carried out. The effect of synthesized compounds containing a 1,3-dioxacyclane fragment on the growth of strains of gram-negative and gram-positive bacteria, lower fungi Candida albicans was studied. It was found that 2-methyl-2-ethyl-4-chloromethyl-1,3-dioxolane, containing a chloromethyl group, has an antimicrobial effect against gram-positive and gram-negative test cultures and weak antifungal activity (minimum inhibitory concentration is 100 μg/mL) against lower fungi Candida albicans. 1-(5-Isopropyl-1,3-dioxan-5-yl)ethanol exhibits antifungal activity (minimum inhibitory concentration is 2 μg/mL) and sharply reduces antimicrobial activity against Klebsiella pneumonia, Staphylococcus aureus, Enterobacter aerogenes (minimum inhibitory concentration is 100 μg/mL), in contrast to the structurally similar 2-methyl-2-ethyl-4-hydroxymethyl-1,3-dioxolane, which did not show similar properties. 5-Acyl-5-isopropyl-1,3-dioxane, containing a carbonyl group in its structure, showed antimicrobial activity (minimum inhibitory concentration is 25 μg/mL) against gram-negative test cultures, with the exception of Pseudomonas aeruginosa. Heterocycles (2-methyl-2-ethyl-4-chloromethyl-, 2-isobutyl-2,4-dimethyl-, 2-methyl-2-isobutyl-4-chloromethyl- and 2-methyl-2-isobutyl-4-hydroxymethyl-1,3-dioxolane) at concentrations up to 100 μg/mL did not inhibit the vital activity of the studied bacteria and lower fungi. The results obtained show the prospect of continuing the search for new antimicrobial and antifungal drugs of the series of 1,3-dioxacycloalkanes, the structure of which is fundamentally different from the known antibacterial drugs.

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