Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles
Abstract
:1. Introduction
2. Results
2.1. Synthesis of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles
2.2. Application of the Prepared Catalysts 9–11 and 14
2.3. Antiproliferative Activities
3. Discussion
4. Materials and Methods
4.1. General Methods
4.2. General Procedure for the Preparation of 3, 4 and 5
4.3. General Procedure for the Preparation of 6, 7 and 8
4.4. General Procedure for the Preparation of 12 and 15
4.5. General Procedure for the Preparation of 13 and 16
4.6. General Procedure for Dihydroxylation
4.7. Antiproliferative Assay
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
DCM | dichloromethane |
CDI | 1,1′-carbonyldiimidazol |
TBAF | tetrabutylammonium fluoride |
NMO | 4-methylmorpholine N-oxide |
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Entry | Catalyst | Yield (%) a | ee (%) b | Configuration of the Major Enantiomer c |
---|---|---|---|---|
1 | 9 | 87 | 74 | S |
2 | 10 | 85 | 62 | S |
3 | 11 | 86 | 50 | S |
4 | 14 | 83 | 70 | S |
Analog | Conc. (µM) | Inhibition (%) ± SEM [Calculated IC50 Value (µM)] | |||
---|---|---|---|---|---|
HeLa | A2780 | MCF7 | MDA-MB-231 | ||
3 | 10 | 29.83 ± 1.65 | 96.66 ± 0.23 | 35.07 ± 2.64 | 19.06 ± 2.98 |
30 | 98.46 ± 0.08 | 96.60 ± 0.37 | 93.00 ± 0.68 | 84.58 ± 1.87 | |
[12.23] | [1.44] | [12.37] | [16.47] | ||
4 | 10 | 37.96 ± 2.20 | 96.28 ± 0.32 | 49.99 ± 0.80 | 33.33 ± 1.94 |
30 | 98.17 ± 0.19 | 96.82 ± 0.18 | 96.08 ± 0.52 | 89.95 ± 0.90 | |
[11.46] | [1.91] | [10.02] | [13.02] | ||
5 | 10 | 21.94 ± 2.94 | 91.95 ± 0.26 | 28.62 ± 1.98 | 20.31 ± 1.45 |
30 | 96.31 ± 0.33 | 93.77 ± 0.27 | 85.27 ± 1.84 | 58.06 ± 1.75 | |
[13.62] | [2.05] | [14.54] | [24.28] | ||
6 | 10 | – * | 56.80 ± 3.18 | 17.30 ± 1.74 | 19.61 ± 2.23 |
30 | 47.39 ± 2.99 | 93.34 ± 0.69 | 23.87 ± 2.37 | 29.68 ± 2.54 | |
7 | 10 | – | 15.35 ± 1.79 | 19.80 ± 1.99 | – |
30 | 24.18 ± 2.42 | 36.92 ± 1.39 | 23.44 ± 1.86 | 24.66 ± 1.38 | |
8 | 10 | – | 12.18 ± 1.70 | 14.62 ± 2.49 | 11.71 ± 0.74 |
30 | 12.31 ± 2.25 | 36.58 ± 1.38 | 35.75 ± 2.79 | 20.27 ± 2.62 | |
9 | 10 | – | – | – | 11.45 ± 2.75 |
30 | 10.83 ± 2.40 | 34.56 ± 1.83 | – | 21.57 ± 1.69 | |
10 | 10 | – | 17.93 ± 1.06 | – | 11.43 ± 1.68 |
30 | 26.01 ± 0.74 | 48.27 ± 0.64 | 44.00 ± 1.34 | 24.67 ± 2.13 | |
11 | 10 | 12.36 ± 1.23 | – | – | – |
30 | 13.41 ± 1.87 | 28.44 ± 0.92 | 25.32 ± 1.10 | 10.36 ± 2.14 | |
12 | 10 | – | – | – | 15.51 ± 2.77 |
30 | – | 31.13 ± 2.48 | – | 15.92 ± 2.69 | |
13 | 10 | – | 11.76 ± 0.76 | – | – |
30 | – | 48.66 ± 1.97 | – | 18.81 ± 2.59 | |
14 | 10 | – | – | – | – |
30 | – | 29.12 ± 2.32 | 14.46 ± 2.31 | 16.28 ± 1.85 | |
cisplatin | 10 | 42.61 ± 2.33 | 83.57 ± 1.21 | 53.03 ± 2.29 | 67.51 ± 1.01 |
30 | 99.93 ± 0.26 | 95.02 ± 0.28 | 86.90 ± 1.24 | 87.75 ± 1.10 | |
[12.43] | [1.30] | [5.78] | [3.74] |
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Gonda, T.; Bérdi, P.; Zupkó, I.; Fülöp, F.; Szakonyi, Z. Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles. Int. J. Mol. Sci. 2018, 19, 81. https://doi.org/10.3390/ijms19010081
Gonda T, Bérdi P, Zupkó I, Fülöp F, Szakonyi Z. Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles. International Journal of Molecular Sciences. 2018; 19(1):81. https://doi.org/10.3390/ijms19010081
Chicago/Turabian StyleGonda, Tímea, Péter Bérdi, István Zupkó, Ferenc Fülöp, and Zsolt Szakonyi. 2018. "Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles" International Journal of Molecular Sciences 19, no. 1: 81. https://doi.org/10.3390/ijms19010081