A Versatile Strategy for the Synthesis of 4,5-Dihydroxy-2,3-Pentanedione (DPD) and Related Compounds as Potential Modulators of Bacterial Quorum Sensing
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of DPD and Ph-DPD
2.2. Synthesis of DPD-Related Compounds
2.2.1. 1,4- and 1,5-Disubstituted 1,2,3-Triazoles DPD-Derivatives (Series I and II)
2.2.2. 3,5-Disubstituted Isoxazoles DPD-Derivatives (Series III and IV)
2.3. Biological Evaluation of Synthetized Compounds
3. Experimental
3.1. Chemistry
3.2. Synthesis of DPD and Ph-DPD
3.3. General Procedures for the Synthesis of 1,4- and 1,5-Disubstituted Triazoles DPD-Derivatives (Series I and II)
3.4. General Procedures for the Synthesis of 3,5-Disubstituted Isoxazoles DPD Derivatives (Series III and IV)
3.5. Biology
3.5.1. LsrK Overexpression and Purification
3.5.2. DPD Activity Evaluation
3.5.3. Screening of DPD-Related Compounds
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are all available from the authors. |
Entry | Solvent | Oxidant and eq | Time | Yield (%) |
---|---|---|---|---|
1 | Acetone | KMnO4/NaHCO3/MgSO4 3.8/0.6/2.0 | Overnight | No reaction |
2 | Acetone | KMnO4/NaHCO3/MgSO4 3.9/0.6/4.2 | Overnight | Traces |
3 | CCl4/ACN (1:1) | NaIO4/RuO2·H2O 2.2 eq/2.5% mol | 3 h | Traces |
4 | CCl4/ACN (1:1) | NaIO4/RuO2·H2O 4.4 eq/2.5% mol | 3 h | 23 |
5 | CHCl3/ACN/H2O (1:1:1) | NaIO4/RuO2·H2O 4.4 eq/2.5% mol | 3 h | 52 |
Entry | R1 | Azide, eq | Solvent | Catalyst | Product | Yield (%) a | Ref. |
---|---|---|---|---|---|---|---|
1 | (CH2)2-Ph | 17a, 1.1 | THF | CuI (10% mol) DIPEA (15% mol) | 18a | 58 | [44] |
2 | (CH2)2-Ph | 17a, 1.05 | DCM | CuI (2% mol) DIPEA (4% mol) AcOH (cat) | 18a | 72 | [48] |
3 | (CH2)2-Ph | 17a, 1.0 | t-BuOH/H2O (1:1) | CuSO4·5H2O (5% mol) Na Ascorbate (0.5 eq) | 18a | 89 | [49] |
4 | (CH2)2-Ph | 17a, 1.0 | 1,4-dioxane | (Cp*RuCl(PPh3)2) (2% mol) | 19a | 87 | [50] |
5 | (CH2)-Ph | 17b, 1.0 | t-BuOH/H2O (1:1) | CuSO4·5H2O (5% mol) Na Ascorbate (0.5 eq) | 18b | 60 | [49] |
6 | (CH2)2-o-F-Ph | 17c, 1.0 | t-BuOH/H2O (1:1) | CuSO4·5H2O (5% mol) Na Ascorbate (0.5 eq) | 18c | 62 | [49] |
7 | (CH2)2-m-Pyr | 17d, 1.0 | t-BuOH/H2O (1:1) | CuSO4·5H2O (5% mol) Na Ascorbate (0.5 eq) | 18d | 88 | [49] |
8 | (CH2)5-CN | 17e, 1.0 | t-BuOH/H2O (1:1) | CuSO4·5H2O (5% mol) Na Ascorbate (0.5 eq) | 18e | 72 | [49] |
9 | (CH2)2-CyH | 17f, 1.0 | t-BuOH/H2O (1:1) | CuSO4·5H2O (5% mol) Na Ascorbate (0.5 eq) | 18f | 73 | [49] |
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Stotani, S.; Gatta, V.; Medda, F.; Padmanaban, M.; Karawajczyk, A.; Tammela, P.; Giordanetto, F.; Tzalis, D.; Collina, S. A Versatile Strategy for the Synthesis of 4,5-Dihydroxy-2,3-Pentanedione (DPD) and Related Compounds as Potential Modulators of Bacterial Quorum Sensing. Molecules 2018, 23, 2545. https://doi.org/10.3390/molecules23102545
Stotani S, Gatta V, Medda F, Padmanaban M, Karawajczyk A, Tammela P, Giordanetto F, Tzalis D, Collina S. A Versatile Strategy for the Synthesis of 4,5-Dihydroxy-2,3-Pentanedione (DPD) and Related Compounds as Potential Modulators of Bacterial Quorum Sensing. Molecules. 2018; 23(10):2545. https://doi.org/10.3390/molecules23102545
Chicago/Turabian StyleStotani, Silvia, Viviana Gatta, Federico Medda, Mohan Padmanaban, Anna Karawajczyk, Päivi Tammela, Fabrizio Giordanetto, Dimitrios Tzalis, and Simona Collina. 2018. "A Versatile Strategy for the Synthesis of 4,5-Dihydroxy-2,3-Pentanedione (DPD) and Related Compounds as Potential Modulators of Bacterial Quorum Sensing" Molecules 23, no. 10: 2545. https://doi.org/10.3390/molecules23102545