Macrooxazoles A–D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus Phoma macrostoma
Abstract
1. Introduction
2. Results and Discussion
2.1. Structure Elucidation of Compounds 1–6
2.2. Biological Activities
3. Materials and Methods
3.1. General Experimental Procedure
3.2. Fungal Material
3.3. Small-Scale Fermentation and Extraction
3.4. Scale Up of Production in Shake Flask Batches and Extraction
3.5. Isolation of Compounds 1–6
3.6. Physico-Chemical Characteristics of Compounds 1–6
3.7. Synthesis of Macrocidin Z (6)
3.8. Antimicrobial Assay
3.9. Cytotoxicity Assay
3.10. Biofilm Inhibition Assay
3.11. Dispersion of Preformed Biofilm
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Position | 6 | Synthetic 6 | ||
---|---|---|---|---|
δC, Type | δH (J in Hz) | δC, Type | δH (J in Hz) | |
2 | 157.4, C | 157.3, C | ||
3/21 | 115.9, CH | 6.69, m | 115.7, CH | 6.71, m |
4/22 | 132.6, CH | 6.98, m | 132.5, CH | 6.97, m |
5 | 127.6, C | 127.3, C | ||
6 | 36.6, CH2 | 3.07, dd (14.1, 3.9) | 36.5, CH2 | 3.07, dd (14.1, 3.9) |
2.90, dd (14.1, 3.3) | 2.89, dd (14.1, 3.1) | |||
7 | 63.8, CH | 4.10, t (3.6) | 63.8, CH | 4.10, m |
9 | 177.3, C | 175.5, C | ||
10 | 102.3, C | 102.1, C | ||
11 | 194.0, C | 191.8, C | ||
12 | 37.2, CH | 3.40, sxt (6.8) | 36.8, C | 3.39, sxt (6.8) |
13 | 35.3, CH2 | 1.16, tdd (12.9, 6.4, 4.3) | 35.1, CH2 | 1.13, m |
1.09, m | ||||
14 | 28.3, CH2 | 0.83, tddd (12.9, 8.5, 6.5, 4.4) | 28.1, CH2 | 0.83, m |
1.32, m | 1.32, m | |||
15 | 33.6, CH2 | 2.06, dq (12.8, 6.2) | 33.4, CH2 | 2.06, m |
1.79, m | 1.79, m | |||
16 | 139.1, CH | 5.67, ddd (15.5, 8.8, 5.9) | 139.0, CH | 5.68, m |
17 | 126.6, CH | 5.26, ddd (15.5, 8.9, 3.8) | 126.7, CH | 5.26, m |
18 | 68.1, CH2 | 4.64, dd (13.4, 8.9) | 67.9, CH2 | 4.64, dd (13.4, 9.5) |
4.53, dd (13.4, 3.8) | 4.53, m | |||
19 | 197.3, C | 197.1, C | ||
20 | 15.4, CH3 | 1.05, d (6.8) | 15.2, CH3 |
Position | 1 | 2 | ||
---|---|---|---|---|
δC, Type | δH (J in Hz) | δC, Type | δH (J in Hz) | |
2 | 164.4, C | - | 165.1, C | - |
4 | 129.0, C | - | 129.6, C | - |
5 | 159.1, C | - | 159.3, C | - |
6 | 34.3, CH2 | 4.00, s | 34.3, CH2 | 4.04, s |
7 | 127.0, C | - | 126.9, C | - |
8 | 131.0, CH | 7.10, d (9.0) | 131.0, CH | 7.12, d (9.0) |
9 | 116.7, CH | 6.73, d (9.0) | 116.7, CH | 6.73, d (9.0) |
10 | 157.9, C | - | 158.0, C | - |
11 | 116.7, CH | 6.73, d (9.0) | 116.7, CH | 6.73, d (9.0) |
12 | 131.0, CH | 7.10, d (9.0) | 131.0, CH | 7.12, d (9.0) |
13 | 163.9, C | - | 163.6, C | - |
14 | 52.4, CH3 | 3.87, s | 52.6, CH3 | 3.88, s |
15 | 30.8, CH2 | 3.19, t (6.5) | 67.3, CH | 5.33, t (6.5) |
16 | 60.6, CH2 | 3.80, t (6.5) | 65.1, CH2 | 3.73, dd (11, 6.5) 3.78, dd (11, 6.5) |
Position | 3 | 4 | ||
---|---|---|---|---|
δC, Type | δH (J in Hz) | δC, Type | δH (J in Hz) | |
2 | 164.8, C | - | 165.3, C | - |
4 | 128.1, C | - | 133.0, C | - |
5 | 155.6, C | - | 155.1, C | - |
6 | 34.3, CH2 | 4.04, s | 34.2, CH2 | 4.00, s |
7 | 126.8, C | - | 126.6, C | |
8 | 131.0, CH | 7.12, d (9.0) | 131.0, CH | 7.08, d (9.0) |
9 | 116.8, CH | 6.75, d (9.0) | 116.7, CH | 6.73, d (9.0) |
10 | 158.0, C | - | 158.0, C | - |
11 | 116.8, CH | 6.75, d (9.0) | 116.7, CH | 6.73, d (9.0) |
12 | 131.0, CH | 7.12, d (9.0) | 131.0, CH | 7.08, d (9.0) |
13 | 163.4, C | - | 163.2, C | - |
14 | 52.6, CH3 | 3.89, s | 52.8, CH3 | 3.92, s |
15 | 123.2, CH | 7.14, dd (17.5, 11.5) | 44.8, CH | 4.51, t (3.5) |
16 | 121.0, CH2 | 5.58, dd (11.5, 1.1) 5.96, dd (17.5, 1.1) | 48.9 *, CH2 | 3.22, dd (3.5, 1.6) |
Compounds | Inhibition of Biofilm Formation (%) | Destruction of Preformed Biofilm (%) |
---|---|---|
1 | - | - |
2 | 65 (250 µg/mL) 43 (125 µg/mL) | 36 (250 µg/mL) 31 (125 µg/mL) |
3 | 75 (250 µg/mL) 59 (125 µg/mL) | 57 (250 µg/mL) 48 (125 µg/mL) |
4 | n.t | n.t |
5 | 79 (250 µg/mL) 77 (62.5 µg/mL) 61 (15.6 µg/mL) | 75 (250 µg/mL) 65 (62.5 µg/mL) 31 (15.6 µg/mL) |
6 | 76 (250 µg/mL) 70 (62.5 µg/mL) 19 (15.6 µg/mL) | 73 (250 µg/mL) 59 (62.5 µg/mL) 40 (15.6 µg/mL) |
Microporenic acid A | 83 (250 µg/mL) 81 (62.5 µg/mL) 48 (15.6 µg/mL) | 71 (250 µg/mL) 70 (62.5 µg/mL) 39 (15.6 µg/mL) |
Sample Availability: Samples of the compounds are available from the authors. | |
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Matio Kemkuignou, B.; Treiber, L.; Zeng, H.; Schrey, H.; Schobert, R.; Stadler, M. Macrooxazoles A–D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus Phoma macrostoma. Molecules 2020, 25, 5497. https://doi.org/10.3390/molecules25235497
Matio Kemkuignou B, Treiber L, Zeng H, Schrey H, Schobert R, Stadler M. Macrooxazoles A–D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus Phoma macrostoma. Molecules. 2020; 25(23):5497. https://doi.org/10.3390/molecules25235497
Chicago/Turabian StyleMatio Kemkuignou, Blondelle, Laura Treiber, Haoxuan Zeng, Hedda Schrey, Rainer Schobert, and Marc Stadler. 2020. "Macrooxazoles A–D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus Phoma macrostoma" Molecules 25, no. 23: 5497. https://doi.org/10.3390/molecules25235497
APA StyleMatio Kemkuignou, B., Treiber, L., Zeng, H., Schrey, H., Schobert, R., & Stadler, M. (2020). Macrooxazoles A–D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus Phoma macrostoma. Molecules, 25(23), 5497. https://doi.org/10.3390/molecules25235497