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Solvent-free one-pot synthesis of polysubstituted tetrahydropyrimidines and their antioxidant and antimicrobial properties

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Abstract

A versatile and highly efficient one-pot multicomponent approach for the synthesis of novel multisubstituted tetrahydropyrimidine (dimethyl/diethyl-1,3-disubstituted-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate) derivatives catalyzed by Bromo(dimethylsulfonium) bromide under solvent-free conditions has been developed. The protocol is eco-friendly, operationally simple, and proceeds in short reaction time, providing high-yield, high-purity (90–95 %) stable target compounds without any side products. Further, the scope of this protocol extended to aliphatic substrates, thus establishing the versatility of the catalyst. The lead compounds were screened for antioxidant and antimicrobial activities. Among them, compounds 4a, 4d, 4e, 4j exhibited excellent antibacterial activity when compared with the standard gentamycin. Compounds 4e and 4k exhibited excellent antifungal activity in comparison with the standard itraconazole. The results of this study revealed that all synthesized compounds were significantly scavenged DPPH free radicals in a concentration-dependent manner. The IC50 values of the compounds is between 13.28 and 23.16 µM when compared with the standard ascorbic acid. Compound 4f was found to be a good antioxidant.

Graphical abstract

The synthesis of polysubstituted tetrahydropyrimidines (dimethyl/diethyl-1,3-disubstituted-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate) derivatives from but-2-ynedioates, amines, and formaldehyde via a one-pot multicomponent reaction is reported. The reactions were performed under solvent-free and mild conditions with shorter reaction times, high purity, and high yield. The obtained products are interesting heterocyclic compounds containing ester functional groups and exhibited excellent antibacterial activity and moderate-to-good antioxidant properties.

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Acknowledgments

The authors are thankful to DST (SR/WOS-A/CS-66/2011), UGC (RGNF), New Delhi, for financial support. MS is thankful to CSIR-IICT for providing laboratory facility, UCPSc, Kakatiya university for biological evaluation.

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Authors and Affiliations

  1. Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500607, India

    Shailaja Myadaraboina, Manjula Alla & Arunadevi Parlapalli

  2. Department of Medicinal Chemistry, UCPSc, Kakatiya University, Warangal, India

    Sarangapani Manda

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  1. Shailaja Myadaraboina
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  2. Manjula Alla
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  3. Arunadevi Parlapalli
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  4. Sarangapani Manda
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Correspondence to Shailaja Myadaraboina.

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Myadaraboina, S., Alla, M., Parlapalli, A. et al. Solvent-free one-pot synthesis of polysubstituted tetrahydropyrimidines and their antioxidant and antimicrobial properties. Res Chem Intermed 42, 923–937 (2016). https://doi.org/10.1007/s11164-015-2063-9

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  • DOI: https://doi.org/10.1007/s11164-015-2063-9

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