Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization of Reaction Conditions
Entry | Temperature (°C) | Solvent | Catalyst (mol%) | Time (h) | Yield a (%) | ee b (%) |
---|---|---|---|---|---|---|
1 | r.t. | THF | 10 | 72 | 34 | 30 |
2 | Reflux | THF | 10 | 2 | - | - |
3 | r.t. | PhMe | 10 | 72 | 52 | 34 |
4 | Reflux | PhMe | 10 | 12 | 54 | 26 |
5 | r.t. | Acetone | 10 | 72 | 38 | 20 |
6 | r.t. | DCM | 10 | 72 | 61 | 78 |
7 | 35 | DCM | 10 | 24 | 67 | 56 |
8 | r.t. | DCM | 5 | 96 | 48 | 76 |
9 | r.t. | DCM | 20 | 72 | 72 | 78 |
Entry | Products | R | R1 | Time (h) a | Yield (%) b | ee (%) c |
---|---|---|---|---|---|---|
1 | 5ac | 6-H | −CH3 | 72 | 82 | 56 |
2 | 5bc | 6-H | −C2H5 | 72 | 80 | 80 |
3 | 5cc | 6-H | −C3H7 | 96 | 78 | 76 |
4 | 5dc | 6-H | −CH2C6H5 | 96 | 76 | 92 |
5 | 5ec | 6-Cl | −CH3 | 72 | 85 | 64 |
6 | 5fc | 6-Cl | −C2H5 | 72 | 86 | 82 |
7 | 5gc | 6-Cl | −C3H7 | 96 | 82 | 80 |
8 | 5hc | 6-Cl | −CH2C6H5 | 96 | 78 | >99 |
9 | 5ic | 6-OCH3 | −CH3 | 72 | 81 | 80 |
10 | 5jc | 6-OCH3 | −C2H5 | 72 | 80 | 80 |
11 | 5kc | 6-OCH3 | −C3H7 | 96 | 79 | 70 |
12 | 5lc | 6-OCH3 | −CH2C6H5 | 96 | 75 | 89 |
13 | 5mc | 6-CH3 | −CH3 | 72 | 81 | 78 |
14 | 5nc | 6-CH3 | −C2H5 | 72 | 76 | 76 |
15 | 5oc | 6-CH3 | −C3H7 | 96 | 76 | 80 |
16 | 5pc | 6-CH3 | −CH2C6H5 | 96 | 72 | 86 |
2.2. Antifungal Activity
Entry | Compound | Inhibition rate a (%) | |||||
---|---|---|---|---|---|---|---|
G. zeae | C. mandshurica | F. oxysporum | P. sasakii | P. infestans | S. sclerotiorum | ||
1 | 5dr | 16.00 ± 0.1 | 9.76 ± 0.5 | 47.04 ± 1.1 | 38.16 ± 1.84 | 13.06 ± 1.5 | 37.42 ± 0.62 |
2 | 5br | 11.67 ± 0.4 | 10.18 ± 0.7 | 37.17 ± 1.1 | 30.04 ± 2.31 | 9.70 ± 0.8 | 21.29 ± 0.76 |
3 | 5cr | 6.03 ± 0.7 | 10.18 ± 0.8 | 19.74 ± 1.5 | 18.37 ± 1.18 | 4.1 ± 0.7 | 3.33 ± 0.5 |
4 | 5dr | 40.67 ± 0.9 | 41.44 ± 0.7 | 60.53 ± 2.2 | 10.11 ± 1.22 | 1.12 ± 0.7 | 6.67 ± 0.6 |
5 | 5er | 3.33 ± 0.5 | 11.66 ± 0.5 | 25.99 ± 1.1 | 16.01 ± 2.31 | 2.33 ± 0.8 | 3.20 ± 0.4 |
6 | 5fr | 8.67 ± 0.5 | 16.45 ± 0.7 | 30.59 ± 0.7 | 18.37 ± 1.23 | 2.33 ± 0.8 | 2.30 ± 1.3 |
7 | 5gr | 4.20 ± 0.5 | 13.13 ± 1.1 | 16.78 ± 2.3 | 9.80 ± 0.69 | 1.03 ± 0.8 | 5.67 ± 0.8 |
8 | 5hr | 6.30 ± 0.7 | 11.66 ± 1.6 | 13.82 ± 2.3 | 13.18 ± 1.26 | 3.33 ± 0.5 | 3.33 ± 0.5 |
9 | 5ir | 9.67 ± 0.9 | 18.97 ± 1.0 | 42.76 ± 2.6 | 11.21 ± 2.10 | 6.67 ± 0.6 | 21.29 ± 0.76 |
10 | 5jr | 11.67 ± 0.6 | 12.71 ± 1.0 | 16.78 ± 1.7 | 13.07 ± 0.84 | 3.20 ± 0.4 | 3.33 ± 0.5 |
11 | 5kr | 4.67 ± 0.7 | 11.23 ± 1.2 | 16.45 ± 1.5 | 15.90 ± 1.24 | 2.30 ± 1.3 | 6.67 ± 0.6 |
12 | 5lr | 0.67 ± 0.6 | 17.18 ± 1.1 | 10.53 ± 2.1 | 3.33 ± 0.5 | 5.67 ± 0.8 | 3.20 ± 0.4 |
13 | 5mr | 1.02 ± 0.7 | 10.87 ± 0.8 | 10.86 ± 1.2 | 6.67 ± 0.6 | 3.33 ± 0.5 | 2.30 ± 1.3 |
14 | 5nr | 4.33 ± 0.8 | 10.50 ± 0.8 | 14.14 ± 0.5 | 3.20 ± 0.4 | 6.67 ± 0.6 | 5.67 ± 0.8 |
15 | 5or | 4.33 ± 0.8 | 19.36 ± 1.5 | 14.14 ± 1.9 | 2.30 ± 1.3 | 3.20 ± 0.4 | 3.33 ± 0.5 |
16 | 5pr | 3.33 ± 0.8 | 19.39 ± 0.3 | 29.93 ± 1.0 | 5.67 ± 0.8 | 2.30 ± 1.3 | 6.67 ± 0.6 |
17 | Hymexazole b | 55.54 ± 3.9 | 49.61 ± 7.8 | 56.12 ± 4.1 | 51.21 ± 5.9 | 68.22 ± 2.4 | 77.51 ± 3.9 |
18 | DMSO | 0 | 0 | 0 | 0 | 0 | 0 |
3. Experimental
3.1. Instruments and Chemicals
3.2. Synthesis
3.2.1. General Methods for Preparation of 3a–d
3.2.2. Characterization of 3a–d
3.2.3. General Method for the Preparation of 5a–p
3.2.4. Characterization of 5a–p
3.3. Antifungal Activity Section
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Xiao, H.; Wu, F.; Shi, L.; Chen, Z.; Su, S.; Tang, C.; Wang, H.; Li, Z.; Li, M.; Shi, Q. Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties. Molecules 2014, 19, 3955-3972. https://doi.org/10.3390/molecules19043955
Xiao H, Wu F, Shi L, Chen Z, Su S, Tang C, Wang H, Li Z, Li M, Shi Q. Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties. Molecules. 2014; 19(4):3955-3972. https://doi.org/10.3390/molecules19043955
Chicago/Turabian StyleXiao, Han, Fang Wu, Li Shi, Zhiwei Chen, Shihu Su, Chenghao Tang, Hongtao Wang, Zhining Li, Meichuan Li, and Qingcai Shi. 2014. "Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties" Molecules 19, no. 4: 3955-3972. https://doi.org/10.3390/molecules19043955