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Synthesis, antimicrobial and antioxidant activity of novel 1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acids, esters, and amides thereof

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Abstract

A preparatively convenient and efficient method is proposed for the synthesis of novel 1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acids, based on the reaction of (3-oxopiperazine-2-ylidene)ethanoates with 2-bromo-1,1-diethoxyethane and accomplished through the stage of intermediate methyl 1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylates, which were also isolated as individual compounds. A method of directly transforming 1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acids into 1-oxo-N-(alkyl)aryl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamides via the former’s interaction with aliphatic and aromatic amines in the presence of DIPEA and HATU was developed, with yields of 31–78%. A reliable structural determination of all the synthesized compounds has been performed by elemental analysis and a number of spectroscopic methods (1H and 13C NMR, HPLC/MS) as well as by X-ray diffraction analysis. Biological screening of all types of synthesized compounds revealed their moderate antibacterial and antifungal activity. The antioxidant effect level of the most active carboxamides was in the range of 59.3–74.5%, as compared to ascorbic acid (97.3%).

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Data availability

We declare that the data supporting the findings of this study are available within the paper and its Supplementary Information files. Should any raw data files be needed in another format, they are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to Enamine Ltd (Kyiv, Ukraine) for support.

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Authors and Affiliations

  1. Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Academician Kukhar Str., Kiev, 02660, Ukraine

    Mariia B. Litvinchuk, Anton V. Bentya & Mykhailo V. Vovk

  2. Bukovinian State Medical University, 2 Teatralnaya Square, Chernivtsi, 58002, Ukraine

    Alina M. Grozav, Nina D. Yakovychuk & Alina O. Palamar

  3. Lesya Ukrainka Volyn National University, 13 Volyi Ave., Lutsk, 43025, Ukraine

    Lesya M. Saliyeva & Nataliia Yu. Slyvka

  4. Institute for Single Crystals, National Academy of Sciences of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine

    Svitlana V. Shishkina

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Litvinchuk, M.B., Bentya, A.V., Grozav, A.M. et al. Synthesis, antimicrobial and antioxidant activity of novel 1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acids, esters, and amides thereof. Monatsh Chem 154, 1145–1159 (2023). https://doi.org/10.1007/s00706-023-03118-8

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