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

doi:10.6023/cjoc202503011

摘要/Abstract

通过靛红、L-脯氨酸反应生成的亚甲胺叶立德可与三氟甲基α,β-不饱和酮发生[3＋2]环加成反应, 高效构建三氟乙酰基取代螺吲哚酮六氢吡咯里嗪. 该反应以廉价的冰乙酸为催化剂, 在甲醇中回流6 h, 以中等至优秀的产率(47%~92%)得到22个螺环化合物, 其中近半数在浓度为50 mg/L时对立枯丝核菌的抑制率超过70%. 当底物α,β-不饱和酮类衍生物1的苯基上对位有取代基时的对应产物(4ba, 4ca, 4da, 4ga)及含有Cl、Br、F取代基时的对应产物(4ia, 4ah, 4ai, 4ak)抑菌活性较好. 对抑菌率在75%以上的6个化合物测定EC₅₀值, 在8.058~19.473 mg/L之间. 相比对照药品, 三氟乙酰基的引入有效提高了螺环化合物对立枯丝核菌的抑制活性.

关键词: 吲哚酮六氢吡咯里嗪, 三氟乙酰基, 抑菌活性

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

引用此文

张睿, 张茵, 李文娟, 韩小强, 赵吉星. 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[J]. 有机化学, 2025, 45(9): 3378-3391.

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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参考文献 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