苯甲酸噻唑酯类衍生物的设计、合成及抗真菌活性评价

doi:10.6023/cjoc202206030

摘要/Abstract

植物病原真菌严重威胁作物安全, 迫切需要开发新型高效低毒的杀菌剂. 因此, 设计、合成了一系列新型苯甲酸噻唑酯衍生物. 体外抗真菌活性筛选结果表明, 化合物3、5和8对灰霉病菌和核盘病菌均表现出良好的抗真菌活性. 其中化合物8对灰霉病菌和核盘病菌的EC₅₀值分别为13.82和3.66 mg/L. 初步的生理生化实验结果表明化合物8对菌丝细胞膜造成一定程度的损伤.

关键词: 苯甲酸, 噻唑, 抗真菌活性, 核盘病菌, 灰霉病菌

Plant pathogenic fungi seriously threaten agricultural production, and there is an urgent need to develop new high efficiency and low toxicity fungicides. In this article, a series of new thiazole benzoate derivatives are designed and synthesized. The preliminary screening results showed that 1-(4,5-dimethylthiazol-2-yl)-2-methylpropyl benzoate (3), (3- chlorophenyl)(4,5-dimethylthiazol-2-yl)methyl benzoate (5), and (4,5-dimethylthiazol-2-yl)(m-tolyl)methyl benzoate (8) showed good inhibitory activities against Botrytis cinerea and Sclerotinia sclerotiorum. Among them, compound 8 has the best inhibitory activity against Botrytis cinerea and Sclerotinia sclerotiorum with EC₅₀ values of 13.82 and 3.66 mg/L, respectively. Preliminary physiological and biochemical experiments showed that compound 8 caused certain damage to Sclerotinia sclerotiorum cell membrane.

Key words: benzoicacid, thiazole, antifungal activity, Sclerotinia sclerotiorum, Botrytis cinerea

引用此文

李猛, 夏东国, 王云霄, 程祥, 巩杰秀, 陈耀, 吕献海. 苯甲酸噻唑酯类衍生物的设计、合成及抗真菌活性评价[J]. 有机化学, 2023, 43(2): 686-696.

Meng Li, Dongguo Xia, Yunxiao Wang, Xiang Cheng, Jiexiu Gong, Yao Chen, Xianhai Lü. Design, Synthesis and Antifungal Bioactivity Evaluation of Thiazole Benzoate Derivatives[J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 686-696.

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参考文献 30

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Compd.	R¹	R²		Inhibition rate^a/%
Compd.	R¹	R²		B. cinerea^b	V. mali^c	S. sclerotiorum^d
1	Phenyl	H		15.4±0.7	25.8±1.2	30.2±1.3
2	1-Naphthyl	H		45.6±0.9	16.9±1.4	10.5±1.8
3	Isopropyl	H		72.3±1.5	72.6±0.9	83.2±1.1
4	2-Cl-Phenyl	H		22.6±1.5	41.3±0.8	20.1±0.8
5	3-Cl-Phenyl	H		77.4±2.2	38.7±1.6	56.0±1.4
6	4-Cl-Phenyl	H		32.3±1.1	12.9±0.7	26.3±2.9
7	2-CH₃-Phenyl	H		13.1±2.4	21.6±1.2	43.5±0.9
8	3-CH₃-Phenyl	H		95.3±3.5	61.2±1.8	94.9±1.6
9	4-CH₃-Phenyl	H		23.0±1.5	31.5±1.4	18.4±0.7
10	Isopropyl	2-Cl		30.5±0.9	61.5±0.3	20.1±0.3
11	Isopropyl	3-Cl		86.9±2.0	53.4±2.5	90.9±1.1
12	Isopropyl	4-Cl		83.3±1.3	41.9±2.2	85.2±0.3
13	Isopropyl	2-CH₃		16.4±0.5	63.3±1.0	67.6±1.4
14	Isopropyl	3-CH₃		90.6±0.7	81.6±2.4	88.2±2.1
15	Isopropyl	4-CH₃		44.3±1.9	65.3±2.0	65.2±1.6
16	Isopropyl	2-CF₃		19.1±0.6	61.2±1.3	63.8±0.3
17	Isopropyl	3-CF₃		48.3±1.3	61.6±0.5	33.6±0.6
18	Isopropyl	4-CF₃		30.6±1.7	57.5±1.1	65.0±1.2
19	3-Cl-Phenyl	2-Cl		82.2±0.6	55.1±1.9	56.0±1.8
20	3-Cl-Phenyl	3-Cl		11.5±0.5	30.6±0.7	5.1±1.2
21	3-Cl-phenyl	4-Cl		82.9±2.0	51.0±1.5	85.3±0.9
22	3-Cl-Phenyl	2-CH₃		88.2±1.5	12.3±0.3	95.1±1.4
23	3-Cl-Phenyl	3-CH₃		16.4±1.9	9.8±1.3	61.6±0.4
24	3-Cl-Phenyl	4-CH₃		40.1±0.8	8.2±1.4	81.6±0.2
25	3-Cl-Phenyl	2-CF₃		45.3±9.5	14.5±0.2	56.2±1.3
26	3-Cl-Phenyl	3-CF₃		35.8±1.2	16.2±0.6	40.8±1.8
27	3-Cl-Phenyl	4-CF₃		21.5±0.4	65.1±2.2	30.8±1.6
28	3-CH₃-Phenyl	2-Cl		84.4±0.6	55.6±1.2	26.4±1.3
30	3-CH₃-Phenyl	4-Cl		60.9±1.2	36.9±0.5	40.6±0.7
31	3-CH₃-Phenyl	2-CH₃		57.3±2.0	45.4±1.3	35.1±0.3
32	3-CH₃-Phenyl	3-CH₃		56.7±0.7	26.4±0.5	16.7±1.4
Compd.	R¹	R²	Inhibition rate^a/%
Compd.	R¹	R²	B. cinerea^b		V. mali^c	S. sclerotiorum^d
33	3-CH₃-Phenyl	4-CH₃	44.3±0.5		61.0±2.2	19.2±2.1
34	3-CH₃-Phenyl	2-CF₃	58.0±1.5		20.3±0.4	15.6±1.5
35	3-CH₃-Phenyl	3-CF₃	65.4±1.9		9.1±1.5	6.4±0.5
36	3-CH₃-Phenyl	4-CF₃	45.6±1.3		30.7±1.1	46.5±1.8
Boscalid	-	-	100.0		95.3	100.0

Compd.	R¹	R²		Inhibition rate^a/%
Compd.	R¹	R²		B. cinerea^b	V. mali^c	S. sclerotiorum^d
1	Phenyl	H		15.4±0.7	25.8±1.2	30.2±1.3
2	1-Naphthyl	H		45.6±0.9	16.9±1.4	10.5±1.8
3	Isopropyl	H		72.3±1.5	72.6±0.9	83.2±1.1
4	2-Cl-Phenyl	H		22.6±1.5	41.3±0.8	20.1±0.8
5	3-Cl-Phenyl	H		77.4±2.2	38.7±1.6	56.0±1.4
6	4-Cl-Phenyl	H		32.3±1.1	12.9±0.7	26.3±2.9
7	2-CH₃-Phenyl	H		13.1±2.4	21.6±1.2	43.5±0.9
8	3-CH₃-Phenyl	H		95.3±3.5	61.2±1.8	94.9±1.6
9	4-CH₃-Phenyl	H		23.0±1.5	31.5±1.4	18.4±0.7
10	Isopropyl	2-Cl		30.5±0.9	61.5±0.3	20.1±0.3
11	Isopropyl	3-Cl		86.9±2.0	53.4±2.5	90.9±1.1
12	Isopropyl	4-Cl		83.3±1.3	41.9±2.2	85.2±0.3
13	Isopropyl	2-CH₃		16.4±0.5	63.3±1.0	67.6±1.4
14	Isopropyl	3-CH₃		90.6±0.7	81.6±2.4	88.2±2.1
15	Isopropyl	4-CH₃		44.3±1.9	65.3±2.0	65.2±1.6
16	Isopropyl	2-CF₃		19.1±0.6	61.2±1.3	63.8±0.3
17	Isopropyl	3-CF₃		48.3±1.3	61.6±0.5	33.6±0.6
18	Isopropyl	4-CF₃		30.6±1.7	57.5±1.1	65.0±1.2
19	3-Cl-Phenyl	2-Cl		82.2±0.6	55.1±1.9	56.0±1.8
20	3-Cl-Phenyl	3-Cl		11.5±0.5	30.6±0.7	5.1±1.2
21	3-Cl-phenyl	4-Cl		82.9±2.0	51.0±1.5	85.3±0.9
22	3-Cl-Phenyl	2-CH₃		88.2±1.5	12.3±0.3	95.1±1.4
23	3-Cl-Phenyl	3-CH₃		16.4±1.9	9.8±1.3	61.6±0.4
24	3-Cl-Phenyl	4-CH₃		40.1±0.8	8.2±1.4	81.6±0.2
25	3-Cl-Phenyl	2-CF₃		45.3±9.5	14.5±0.2	56.2±1.3
26	3-Cl-Phenyl	3-CF₃		35.8±1.2	16.2±0.6	40.8±1.8
27	3-Cl-Phenyl	4-CF₃		21.5±0.4	65.1±2.2	30.8±1.6
28	3-CH₃-Phenyl	2-Cl		84.4±0.6	55.6±1.2	26.4±1.3
30	3-CH₃-Phenyl	4-Cl		60.9±1.2	36.9±0.5	40.6±0.7
31	3-CH₃-Phenyl	2-CH₃		57.3±2.0	45.4±1.3	35.1±0.3
32	3-CH₃-Phenyl	3-CH₃		56.7±0.7	26.4±0.5	16.7±1.4
Compd.	R¹	R²	Inhibition rate^a/%
Compd.	R¹	R²	B. cinerea^b		V. mali^c	S. sclerotiorum^d
33	3-CH₃-Phenyl	4-CH₃	44.3±0.5		61.0±2.2	19.2±2.1
34	3-CH₃-Phenyl	2-CF₃	58.0±1.5		20.3±0.4	15.6±1.5
35	3-CH₃-Phenyl	3-CF₃	65.4±1.9		9.1±1.5	6.4±0.5
36	3-CH₃-Phenyl	4-CF₃	45.6±1.3		30.7±1.1	46.5±1.8
Boscalid	-	-	100.0		95.3	100.0

Fungi	Compd.	EC₅₀/(mg•L^-1)	95% confidence interval	Regression equation^a	R^b
B. cinerea	3	32.61	29.13~36.99	y=5.581x-8.446	0.998
	5	31.60	28.24~35.81	y=5.550x-8.323	0.988
	8	13.82	12.27~15.58	y=4.690x-5.349	0.989
	11	21.17	18.97~23.72	y=5.422x-7.188	0.989
	12	21.81	14.06~40.87	y=3.120x-4.176	0.942
	14	15.31	13.56~17.32	y=4.513x-5.347	0.994
	19	21.85	19.01~25.43	y=3.941x-5.010	0.986
	21	23.36	15.85~40.05	y=3.498x-4.787	0.962
	22	19.25	17.11~21.77	y=4.765x-6.120	0.995
	28	23.17	20.27~26.85	y=3.974x-5.420	0.980
	Boscalid	0.88	0.03~1.77	y=2.340x＋0.134	0.971
V. mali	3	30.74	27.42~34.90	y=5.375x-7.996	0.999
	14	15.90	13.82~18.40	y=3.576x-4.296	0.980
	Boscalid	13.44	11.55~16.13	y=3.804x-4.292	0.978
S. sclerotiorum	3	12.07	10.22~14.20	y=2.919x-3.156	0.988
	8	3.66	2.57~4.70	y=2.370x-1.335	0.986
	11	8.79	7.28~10.46	y=2.689x-2.538	0.988
	12	15.74	13.76~18.08	y=3.830x-4.584	0.986
	14	12.38	10.80~14.20	y=3.755x-4.104	0.986
	21	22.90	20.41~25.89	y=5.008x-6.810	0.993
	22	13.81	9.92~19.38	y=5.166x-5.891	0.983
	24	16.59	14.38~19.27	y=3.492x-4.260	0.985
	Boscalid	0.95	0.53~1.35	y=2.052x＋0.049	0.960

Fungi	Compd.	EC₅₀/(mg•L^-1)	95% confidence interval	Regression equation^a	R^b
B. cinerea	3	32.61	29.13~36.99	y=5.581x-8.446	0.998
	5	31.60	28.24~35.81	y=5.550x-8.323	0.988
	8	13.82	12.27~15.58	y=4.690x-5.349	0.989
	11	21.17	18.97~23.72	y=5.422x-7.188	0.989
	12	21.81	14.06~40.87	y=3.120x-4.176	0.942
	14	15.31	13.56~17.32	y=4.513x-5.347	0.994
	19	21.85	19.01~25.43	y=3.941x-5.010	0.986
	21	23.36	15.85~40.05	y=3.498x-4.787	0.962
	22	19.25	17.11~21.77	y=4.765x-6.120	0.995
	28	23.17	20.27~26.85	y=3.974x-5.420	0.980
	Boscalid	0.88	0.03~1.77	y=2.340x＋0.134	0.971
V. mali	3	30.74	27.42~34.90	y=5.375x-7.996	0.999
	14	15.90	13.82~18.40	y=3.576x-4.296	0.980
	Boscalid	13.44	11.55~16.13	y=3.804x-4.292	0.978
S. sclerotiorum	3	12.07	10.22~14.20	y=2.919x-3.156	0.988
	8	3.66	2.57~4.70	y=2.370x-1.335	0.986
	11	8.79	7.28~10.46	y=2.689x-2.538	0.988
	12	15.74	13.76~18.08	y=3.830x-4.584	0.986
	14	12.38	10.80~14.20	y=3.755x-4.104	0.986
	21	22.90	20.41~25.89	y=5.008x-6.810	0.993
	22	13.81	9.92~19.38	y=5.166x-5.891	0.983
	24	16.59	14.38~19.27	y=3.492x-4.260	0.985
	Boscalid	0.95	0.53~1.35	y=2.052x＋0.049	0.960