Synthesis of 2-aminopyridine Lactones and Studies of Their Antioxidant, Antibacterial and Antifungal Properties †
1
Normandie Université France, ENSICAEN, LCMT, UMR CNRS 6507, INC3 M, FR 3038, Labex EMC3, LabexSynOrg, 6 Bd Maréchal Juin, 14050 Caen, France
2
Laboratoire de Catalyse et Synthèse en Chimie Organique, Faculté des Sciences, Université Abou-Bakr Belkaid, BP 119, Tlemcen 13000, Algeria
*
Author to whom correspondence should be addressed.
†
Presented at the 25th International Electronic Conference on Synthetic Organic Chemistry, 15–30 November 2021. Available online: https://ecsoc-25.sciforum.net/ .
Chem. Proc. 2022, 8(1), 94; https://doi.org/10.3390/ecsoc-25-11709
Published: 15 November 2021
(This article belongs to the Proceedings of The 25th International Electronic Conference on Synthetic Organic Chemistry)
Abstract
:In the present work, the synthesis and biological activities of substituted 2-aminopyridine δ-lactone derivatives were achieved. 4,6,6-trimethyl-2-oxo-5,6-dihydro-2H-pyran-3-carbonitrile was synthesised from 4-hydroxy-4-methylpentan-2-one, followed by its transformation in enaminonitrile with DMFDMA. The antioxidant effects of substituted 2-aminopyridine δ-lactone derivatives were evaluated through DPPH assay and revealed a great antioxidant capacity. The antifungal and antibacterial activities were investigated by disc diffusion method against clinical Gram-negative bacteria and against clinical fungi. The study shows moderate to very good antibacterial and antifungal activities for the new substituted 2-aminopyridine δ-lactone derivatives.
1. Introduction
Substituted 2-aminopyridine δ-lactone derivatives were achieved. 4,6,6-trimethyl-2-oxo-5,6-dihydro-2H-pyran-3-carbonitrile (1) was synthesised from 4-hydroxy-4-methylpentan-2-one [1] (Figure 1), followed by its transformation in enaminonitrile with DMFDMA [1].
The compound 3 was prepared by the reaction of δ-lactone nitrile «4,6,6-trimethyl-2-oxo-5,6-dihydro-2H-pyran-3-carbonitrile » 1 with dimethylformamide dimethylacetal DMFDMA in stoichiometric amounts. The reaction was performed at room temperature during 24 h and afforded good overall yield (72%) [1] according the Figure 2.
The reaction of enaminolactone nitrile 3 and primary amines 4a–f in refluxed DMF according to our previous work [1] results in new substituted 2-aminopyridines 5a–f, according Figure 3, results are reported in Table 1.
The reactions between 1 equiv of diamines 6a–c with 2 equiv of enaminolactone nitrile 3 were performed. The mixture was refluxed in DMF during 6 h. After removing of the solvent and purification by column chromatography, we afforded the new original bis-(2-aminopyridines) 7a–c in moderate to good yields (Figure 4, Table 2).
The structure of the compounds 7a–c was confirmed by spectral data (IR, 1H NMR and 13CNMR).
2. Antioxidant Effects
The antioxidant effects of substituted 2-aminopyridine δ-lactone derivatives were evaluated through DPPH assay and revealed a great antioxidant capacity.
For initial screening of antioxidant activity DPPH on TLC was employed [2]. After the qualitative confirmation of antioxidant potential, spectroscopic measurements were made through DPPH assay. The antioxidant proprieties were measured and evidenced in terms of their efficient concentration IC50, as well as their reduction kinetics [3]. Evaluation of the antioxydant activity by the test of DPPH, revealed a great antioxydant capacity for the most of compounds tested with a variation of IC50 between 1.30–3.61 mg/mL and times of reaction of 30 min.
3. Antifungal and Antibacterial Activities
The antifungal and antibacterial activities of 2-aminopyridines and bis-2-aminopyridines were investigated in vitro in order to evaluate their efficacy. The antibacterial activity of the compounds was determined by the disc diffusion method [4,5] against clinical Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa and Gram-positive bacteria: Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The antifungal activity of the compounds was determined by using a direct-contact and agar diffusion test [4] against clinical fungi Aspergillus flavus and Aspergillus ochraceus. The compounds showed moderate to very good antibacterial and antifungal activities, that the 5b, 5d, 5e and 5f presents a best minimal inhibitory concentration (MIC) with 62.5 µg/mL. The Aspergillus ochraceus strain revealed a stronger sensitivity than Aspergillus flavus to all compounds tested, While that the 7c and 7b showed a braod-spectrum antifungal activity again pathogenic Aspergillus ochraceus with an inhibition percentage of 77% and 78%, respectively. Based our results, the compounds of 2-aminopyridines and bis-2-aminopyridines can be considered as a source of novel antibiotic and antifungal.
4. Experimental
In the supplementary informations:
- (A)
- Synthesis and Screening of Antioxidant Potential
- (B)
- Screening of antibacterial and antifungal properties of the compounds.
5. Conclusions
The study shows moderate to very good antibacterial and antifungal activities for the new substituted 2-aminopyridine δ-lactone derivatives.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ecsoc-25-11709/s1.
Author Contributions
Conceptualization, D.V.; Investigation, F.S. and N.B.; Writing—Original draft, N.B. and D.V.; Writing—Review and editing, N.C., N.B. and D.V. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Supplementary Informations in English (parts A and B) https://hal-normandie-univ-archives-ouvertes-fr.ezproxy.u-pec.fr/hal-03510414/document.
Conflicts of Interest
The authors declare no conflict of interest.
References
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Figure 1.
Synthesis of 4,6,6-trimethyl-2-oxo-5,6-dihydro-2H-pyran-3-carbonitrile 1.
Figure 2.
Synthesis of enaminolactone nitrile 3.
Figure 3.
Synthesis of 2-aminopyridines 5a-f from enaminolactone nitrile 3.
Figure 4.
Synthesis of new bis-(2-aminopyridines) 7a–c.
Table 1.
Synthesis of 2-aminopyridine lactones.
| Entry | Enaminolactone | RNH2 | Product | Yield (%) |
|---|---|---|---|---|
| 1 | 3 |  4a |  5a | 95 |
| 2 | 3 |  4b |  5b | 87 |
| 3 | 3 |  4c |  5c | 92 |
| 4 | 3 |  4d |  5d | 96 |
| 5 | 3 |  4e |  5e | 95 |
| 6 | 3 |  4f |  5f | 96 |
The structure of substituted 2-aminopyridine δ-lactones were characterised by spectroscopic methods (IR, 1H NMR, 13C NMR and MS).
Table 2.
Synthesis of bis-2-aminopyridine lactones.
| Entry | RNH2 | Product | Yield (%) | |
|---|---|---|---|---|
| 1 | 3 |  6a |  7a | 57 |
| 2 | 3 |  6b |  7b | 60 |
| 3 | 3 |  6c |  7c | 89 |
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MDPI and ACS Style
Salhi, F.; Cheikh, N.; Villemin, D.; Bar, N. Synthesis of 2-aminopyridine Lactones and Studies of Their Antioxidant, Antibacterial and Antifungal Properties. Chem. Proc. 2022, 8, 94. https://doi.org/10.3390/ecsoc-25-11709
AMA Style
Salhi F, Cheikh N, Villemin D, Bar N. Synthesis of 2-aminopyridine Lactones and Studies of Their Antioxidant, Antibacterial and Antifungal Properties. Chemistry Proceedings. 2022; 8(1):94. https://doi.org/10.3390/ecsoc-25-11709
Chicago/Turabian StyleSalhi, Fadila, Nawel Cheikh, Didier Villemin, and Nathalie Bar. 2022. "Synthesis of 2-aminopyridine Lactones and Studies of Their Antioxidant, Antibacterial and Antifungal Properties" Chemistry Proceedings 8, no. 1: 94. https://doi.org/10.3390/ecsoc-25-11709
APA StyleSalhi, F., Cheikh, N., Villemin, D., & Bar, N. (2022). Synthesis of 2-aminopyridine Lactones and Studies of Their Antioxidant, Antibacterial and Antifungal Properties. Chemistry Proceedings, 8(1), 94. https://doi.org/10.3390/ecsoc-25-11709
