Construction and Antifungal Activity Study of Trifluoroacetyl Substituted Spiro Indolinone-Hexahydropyrrolizine Derivatives

doi:10.6023/cjoc202503011

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (9): 3378-3391.DOI: 10.6023/cjoc202503011 Previous Articles Next Articles

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三氟乙酰基取代螺吲哚酮六氢吡咯里嗪衍生物的构建及抑菌活性研究

张睿^a, 张茵^a, 李文娟^a^,^*(), 韩小强^b^,^*(), 赵吉星^c

^a 石河子大学化学化工学院新疆兵团化工绿色过程重点实验室新疆石河子 832003
^b 石河子大学农学院新疆绿洲农业病虫害治理与植物资源利用重点实验室新疆石河子 832003
^c 石河子大学分析测试中心新疆石河子 832003

收稿日期:2025-04-17 修回日期:2025-05-02 发布日期:2025-05-30
基金资助:
石河子大学高层次人才启动(RCZK2021B08); 石河子大学创新发展专项(CXFZ202303)

Construction and Antifungal Activity Study of Trifluoroacetyl Substituted Spiro Indolinone-Hexahydropyrrolizine Derivatives

Rui Zhang^a, Yin Zhang^a, Wenjuan Li^a^,^*(), Xiaoqiang Han^b^,^*(), Jixing Zhao^c

^a Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, Xinjiang 832003
^b Key Laboratory for Oasis Agricultural Pest Management and Plant Protection Resources Utilization, College of Agriculture, Shihezi University, Shihezi, Xinjiang 832003
^c Analysis and Testing Center, Shihezi University, Shihezi, Xinjiang 832003

Received:2025-04-17 Revised:2025-05-02 Published:2025-05-30
Contact: *E-mail: lwj01_tea@shzu.edu.cn; hanshz@shzu.edu.cn
Supported by:
High Level Talents Launch Project of Shehezi University(RCZK2021B08); Special Project of Innovation and Development of Shehezi University(CXFZ202303)

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Abstract

The azomethine ylide through the reaction of isatin with L-proline, undergoes a [3＋2] cycloaddition reaction with trifluoromethyl α,β-unsaturated ketones. This reaction could efficiently construct trifluoroacetyl substituted spiro indolinone- hexahydropyrrolizine compound. The reaction used inexpensive glacial acetic acid as a catalyst, methanol as solvent, and refluxed for 6 h. A series of spiro compounds were obtained with moderate to excellent yields (47%~92%). Nearly half of the compounds showed an inhibition rate of over 70% against Rhizoctonia solani at a concentration of 50 mg/L. If the product contains para-substituents on the phenyl group of substrate 1 (4ba, 4ca, 4da, 4ga), or if the product contains Cl, Br, F substituents (4ia, 4ah, 4ai, 4ak), the antibacterial activity is better. There are 6 compounds that the initial screening result is greater than 75%. The EC₅₀ values of these compounds are between 8.058 and 19.473 mg/L. Compared to the control drug, the introduction of trifluoroacetyl effectively enhanced the inhibitory activity of spirocyclic compounds against Rhizoctonia solani.

Key words: indolinone hexahydropyrrolizine, trifluoroacetyl, fungicidal activity

Cite this article

Rui Zhang, Yin Zhang, Wenjuan Li, Xiaoqiang Han, Jixing Zhao. Construction and Antifungal Activity Study of Trifluoroacetyl Substituted Spiro Indolinone-Hexahydropyrrolizine Derivatives[J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3378-3391.

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Fig. & Tab. 11

References 8

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Entry	2a/equiv.	3a/equiv.	Cat. (equiv.)	Solvent	Yield^b/%
1	1	1	MeCOOH (0.5)	MeOH	67
2	1.25	1	MeCOOH (0.5)	MeOH	55
3	1	1.25	MeCOOH (0.5)	MeOH	71
4	1	1.5	MeCOOH (0.5)	MeOH	70
5	1.4	1.75	MeCOOH (0.5)	MeOH	69
6	1.6	2	MeCOOH (0.5)	MeOH	79
7	2	2.5	MeCOOH (0.5)	MeOH	77
8	1.6	2	MeCOOH (0.25)	MeOH	89
9	1.6	2	None	MeOH	30
10	1.6	2	HCl (1 mol/L, 0.25)	MeOH	48
11	1.6	2	TsOH (0.25)	MeOH	75
12	1.6	2	TfOH (0.25)	MeOH	81
13	1.6	2	EtCOOH (0.25)	MeOH	81
14^c	1.6	2	MeCOOH (0.25)	MeOH	86
15^c^,^d	1.6	2	MeCOOH (0.25)	MeOH	87
16	1.6	2	MeCOOH (0.25)	Toluene	Trace
17	1.6	2	MeCOOH (0.25)	DCE	Trace
18	1.6	2	MeCOOH (0.25)	1,4-Dioxane	Trace
19	1.6	2	MeCOOH (0.25)	MeCN	57
20	1.6	2	MeCOOH (0.25)	THF	72
21^e^,^f	1.6	2	MeCOOH (0.25)	MeOH	—

Entry	2a/equiv.	3a/equiv.	Cat. (equiv.)	Solvent	Yield^b/%
1	1	1	MeCOOH (0.5)	MeOH	67
2	1.25	1	MeCOOH (0.5)	MeOH	55
3	1	1.25	MeCOOH (0.5)	MeOH	71
4	1	1.5	MeCOOH (0.5)	MeOH	70
5	1.4	1.75	MeCOOH (0.5)	MeOH	69
6	1.6	2	MeCOOH (0.5)	MeOH	79
7	2	2.5	MeCOOH (0.5)	MeOH	77
8	1.6	2	MeCOOH (0.25)	MeOH	89
9	1.6	2	None	MeOH	30
10	1.6	2	HCl (1 mol/L, 0.25)	MeOH	48
11	1.6	2	TsOH (0.25)	MeOH	75
12	1.6	2	TfOH (0.25)	MeOH	81
13	1.6	2	EtCOOH (0.25)	MeOH	81
14^c	1.6	2	MeCOOH (0.25)	MeOH	86
15^c^,^d	1.6	2	MeCOOH (0.25)	MeOH	87
16	1.6	2	MeCOOH (0.25)	Toluene	Trace
17	1.6	2	MeCOOH (0.25)	DCE	Trace
18	1.6	2	MeCOOH (0.25)	1,4-Dioxane	Trace
19	1.6	2	MeCOOH (0.25)	MeCN	57
20	1.6	2	MeCOOH (0.25)	THF	72
21^e^,^f	1.6	2	MeCOOH (0.25)	MeOH	—

Compd.	Inhibitory rate±SE/%
Compd.	Rhizoctonia solani	Cytospora chrysosperma	Fusarium oxysporum
4aa	59.7±2.2	36.1±1.4	55.1±3.4
4ba	70.4±1.6	29.9±1.4	62.9±3.2
4ca	80.2±0.6	54.8±0.4	50.6±1.7
4da	84.1±1.2	30.0±1.9	52.7±0.6
4ea	51.7±1.2	27.6±2.0	56.3±2.1
4fa	50.1±2.9	24.8±1.1	54.0±3.1
4ga	70.3±2.0	51.3±0.7	51.5±1.5
4ha	57.1±2.0	37.6±1.1	60.1±2.3
4ia	72.7±2.1	45.5±1.4	61.6±0.3
4ja	87.8±1.4	41.8±1.0	55.6±1.6
4ab	64.7±3.1	46.7±0.6	56.1±4.4
4ac	67.4±1.4	42.2±1.7	34.6±1.0
4ad	76.6±2.2	41.7±1.1	29.0±1.1
4ae	39.2±3.3	30.0±1.1	25.8±1.0
4af	64.2±1.0	12.0±2.0	46.5±1.2
4ag	38.9±2.1	13.3±0.5	58.8±4.0
4ah	82.5±1.1	54.6±1.1	54.4±1.3
4ai	84.6±0.7	33.0±1.5	51.4±3.0
4aj	65.4±2.1	53.7±0.3	51.3±2.0
4ak	73.5±0.6	38.9±0.5	60.9±0.9
4al	40.3±4.1	45.9±1.2	47.3±1.1
Carbendazim	94.1±1.0	96.4±0.8	97.3±0.8

Compd.	Inhibitory rate±SE/%
Compd.	Rhizoctonia solani	Cytospora chrysosperma	Fusarium oxysporum
4aa	59.7±2.2	36.1±1.4	55.1±3.4
4ba	70.4±1.6	29.9±1.4	62.9±3.2
4ca	80.2±0.6	54.8±0.4	50.6±1.7
4da	84.1±1.2	30.0±1.9	52.7±0.6
4ea	51.7±1.2	27.6±2.0	56.3±2.1
4fa	50.1±2.9	24.8±1.1	54.0±3.1
4ga	70.3±2.0	51.3±0.7	51.5±1.5
4ha	57.1±2.0	37.6±1.1	60.1±2.3
4ia	72.7±2.1	45.5±1.4	61.6±0.3
4ja	87.8±1.4	41.8±1.0	55.6±1.6
4ab	64.7±3.1	46.7±0.6	56.1±4.4
4ac	67.4±1.4	42.2±1.7	34.6±1.0
4ad	76.6±2.2	41.7±1.1	29.0±1.1
4ae	39.2±3.3	30.0±1.1	25.8±1.0
4af	64.2±1.0	12.0±2.0	46.5±1.2
4ag	38.9±2.1	13.3±0.5	58.8±4.0
4ah	82.5±1.1	54.6±1.1	54.4±1.3
4ai	84.6±0.7	33.0±1.5	51.4±3.0
4aj	65.4±2.1	53.7±0.3	51.3±2.0
4ak	73.5±0.6	38.9±0.5	60.9±0.9
4al	40.3±4.1	45.9±1.2	47.3±1.1
Carbendazim	94.1±1.0	96.4±0.8	97.3±0.8

Compd.	Inhibitory rate±SE/%
Compd.	Rhizoctonia solani
5	55.7±1.2
6	52.5±0.9
7	62.9±2.1
8	49.8±1.3
Carbendazim	94.8±0.7

三氟乙酰基取代螺吲哚酮六氢吡咯里嗪衍生物的构建及抑菌活性研究

Construction and Antifungal Activity Study of Trifluoroacetyl Substituted Spiro Indolinone-Hexahydropyrrolizine Derivatives

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Compd.	Regression equation	R²	EC₅₀/(μg•mL^-1)
4ca	y=2.083x-2.288	0.984	12.532
4da	y=2.751x-3.065	0.994	13.010
4ja	y=2.739x-2.483	0.964	8.058
4ad	y=2.763x-3.486	0.985	18.258
4ah	y=3.261x-3.896	0.978	15.657
4ai	y=3.757x-4.842	0.950	19.437
6	y=1.152x-1.833	0.988	38.296
7	y=1.608x-2.312	0.995	27.421
Carbendazim	y=1.207x＋0.476	0.998	0.404

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