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

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 (H-1 and C-13 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%).

Automated summary

A convenient and efficient method for the synthesis of novel 1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acids was proposed. The compounds were synthesized through a reaction between (3-oxopiperazine-2-ylidene)ethanoates and 2-bromo-1,1-diethoxyethane, with intermediate methyl 1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylates also being isolated. Another method to transform the carboxylic acids into carboxamides was developed, achieving yields of 31-78%. The synthesized compounds displayed moderate antimicrobial and antifungal activity, with some of the carboxamides showing antioxidant effects comparable to ascorbic acid.