新型含肟醚结构丁烯内酯类化合物的合成及杀菌活性

doi:10.6023/cjoc202203033

摘要/Abstract

以具有良好杀菌活性的3-乙酰基-4-苯基-1-氧杂螺[4,5]癸-3-烯-2-酮肟为先导化合物, 通过对4-芳环和3-肟基芳环的结构进行多样化修饰, 设计合成了一系列新型含肟醚结构的丁烯内酯类化合物, 它们的化学结构经¹H NMR, ¹³C NMR, 高分辨质谱和晶体X射线衍射确证. 离体杀菌测试结果表明部分目标化合物对水稻纹枯菌、番茄灰霉菌和油菜菌核菌表现出良好的抑菌活性, 如(E)-3-(1-(2-氯苄氧基亚胺基)乙基)-4-(吡啶-2-基)-1-氧杂螺[4,5]癸-3-烯-2-酮(A7)对水稻纹枯菌、番茄灰霉菌和油菜菌核菌的EC₅₀分别为6.02, 8.25和15.70 mg/L, (E)-3-(1-(2-氯苄氧基亚胺基)乙基)-4-(吡啶-4-基)-1-氧杂螺[4,5]癸-3-烯-2-酮(A8)对水稻纹枯菌和油菜菌核菌的EC₅₀值分别为1.31和10.62 mg/L. A7对番茄灰霉菌的孢子萌发具有显著抑制作用, 在100 mg/L浓度下对孢子萌发的抑制率达95%. 活体杀菌测试结果表明A7对番茄灰霉病和水稻纹枯病具有明显的保护活性.

关键词: 3-乙酰基-4-芳基-1-氧杂螺[4,5]癸-3-烯-2-酮, 肟醚, 合成, 杀菌活性

A series of novel butenolide compounds containing oxime ether moiety were designed and synthesized through diversity modification of the benzene ring at 4-phenyl and the 3-oxime ether group based on the fungicidal 3-acetyl-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one oxime ether as the lead structure. Their structures were characterized by ¹H NMR, ¹³C NMR, HR-ESI-MS data and X-ray diffraction. The preliminary in vitro bioassay results indicated that some compounds exhibited good fungicidal activities against Thanatephorus cucumeris, Sclerotinia sclerotiorum and Botrytis cinerea. For example, (E)-3-(1-((2-chlorobenzyloxy)imino)ethyl)-4-(pyridin-2-yl)-1-oxaspiro[4.5]dec-3-en-2-one (A₇) had EC₅₀ values of 6.02, 8.25 and 15.70 mg/L against T. cucumeris, S. sclerotiorum and B. cinerea, (E)-3-(1-((2-chlorobenzyloxy)imino)ethyl)-4-(pyridin-4-yl)-1-oxaspiro[4.5]dec-3-en-2-one (A₈) had EC₅₀ values of 1.31 and 10.62 mg/L against T. cucumeris and S. sclerotiorum, respectively. A₇ had an excellent inhibition against spore germination of B. cinerea, and the inhibition rate was 95% at the concentration of 100 mg/L. The in vivo bioassay results showed that compounds A₇ had a notable protective activity against tomato gray mould and rice sheath blight disease.

Key words: 3-acetyl-4-aryl-1-oxaspiro[4,5]dec-3-en-2-one, oxime ether, synthesis, fungicidal activity

引用此文

张倩, 李益豪, 许磊川, 马好运, 李向东, 王明安. 新型含肟醚结构丁烯内酯类化合物的合成及杀菌活性[J]. 有机化学, 2022, 42(8): 2438-2448.

Qian Zhang, Yihao Li, Leichuan Xu, Haoyun Ma, Xiangdong Li, Ming'an Wang. Synthesis and Fungicidal Activity of Novel Butenolide Compounds Containing Oxime Ether Moiety[J]. Chinese Journal of Organic Chemistry, 2022, 42(8): 2438-2448.

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化合物	R⁴	小麦赤霉菌	油菜菌核菌	辣椒疫霉菌	番茄灰霉菌	水稻纹枯菌
A1	4-NO₂	16.3±2.0	11.3±5.2	3.3±1.2	12.6±3.5	10.6±1.1
A2	4-NO₂	7.2±3.4	21.0±1.0	6.0±3.3	15.3±0.7	15.6±2.3
A3	4-NO₂	10.8±4.7	12.6±2.1	1.9±4.0	10.6±8.3	17.8±0.03
A4	4-NO₂	0.0±2.1	13.3±0.3	0	10.4±5.0	11.7±4.3
A5	4-NO₂	9.0±3.4	55.2±0.5	4.0±0.1	7.0±7.3	20.6±9.2
A6	4-NO₂	18.7±1.6	43.6±0.8	26.2±2.8	12.2±2.4	45.8±3.0
A7	2-Cl	44.3±1.2	82.4±1.0	46.1±0.8	73.0±3.0	70.5±2.0
A8	2-Cl	30.9±1.0	81.9±1.5	21.8±1.6	53.5±2.8	73.5±0.8
A9	2-Cl	3.5±5.3	56.2±2.0	5.3±2.2	25.5±0.9	10.0±3.2
A10	2-Cl	10.8±1.5	41.7±3.8	3.3±2.2	0	29.0±1.7
A11	2-Cl	4.1±5.6	64.9±4.3	4.7±1.1	2.7±2.5	25.7±3.3
A12	2-Cl	5.4±3.1	56.7±3.1	0.0±2.0	48.1±1.8	20.6±3.8
A13	2-Cl	3.6±3.0	58.2±4.1	0.0±2.0	32.6±1.4	4.4±4.1
A14	2-Cl	19.3±1.8	28.9±2.2	14.7±3.2	30.4±6.0	40.1±0.9
A15	4-Br	24.9±1.9	30.2±1.5	7.8±2.6	7.6±2.5	39.5±2.0
A16	4-Br	29.8±1.0	31.7±1.3	23.3±0.2	47.0±3.0	72.5±0.4
A17	3,4-Cl₂	10.9±0.9	0	8.6±2.0	11.4±2.0	0
A18	3,4-Cl₂	12.2±2.2	0	7.9±3.0	22.8±0.5	9.7±7.1
A19	3,4-Cl₂	5.1±2.2	33.3±2.7	4.6±6.0	13.9±4.5	20.0±6.8
A20	3,4-Cl₂	7.0±2.9	0.0±3.3	0.0±2.0	17.8±6.1	6.3±3.2
A21	3,4-Cl₂	0.6±2.9	0	6.0±2.0	5.0±4.4	0
A22	3,4-Cl₂	12.0±3.1	20.6±2.9	6.0±1.0	0	35.9±0.0
A23	4-CF₃	22.9±0.6	23.6±0.8	17.6±3.8	3.8±0.9	37.5±1.0
A24	4-CF₃	27.3±1.9	33.2±0.3	28.0±1.3	37.3±1.9	63.0±0.8
A25	4-OCH₃	21.4±2.8	21.1±2.9	7.3±0.9	11.4±1.7	47.0±1.0
A26	4-OCH₃	20.4±0.6	24.1±1.3	24.9±1.6	13.5±3.3	42.0±1.0
肟菌酯		43.9±1.5	68.6±0.6	2.0±0.0	49.7±0.5	69.8±1.8

化合物	R⁴	小麦赤霉菌	油菜菌核菌	辣椒疫霉菌	番茄灰霉菌	水稻纹枯菌
A1	4-NO₂	16.3±2.0	11.3±5.2	3.3±1.2	12.6±3.5	10.6±1.1
A2	4-NO₂	7.2±3.4	21.0±1.0	6.0±3.3	15.3±0.7	15.6±2.3
A3	4-NO₂	10.8±4.7	12.6±2.1	1.9±4.0	10.6±8.3	17.8±0.03
A4	4-NO₂	0.0±2.1	13.3±0.3	0	10.4±5.0	11.7±4.3
A5	4-NO₂	9.0±3.4	55.2±0.5	4.0±0.1	7.0±7.3	20.6±9.2
A6	4-NO₂	18.7±1.6	43.6±0.8	26.2±2.8	12.2±2.4	45.8±3.0
A7	2-Cl	44.3±1.2	82.4±1.0	46.1±0.8	73.0±3.0	70.5±2.0
A8	2-Cl	30.9±1.0	81.9±1.5	21.8±1.6	53.5±2.8	73.5±0.8
A9	2-Cl	3.5±5.3	56.2±2.0	5.3±2.2	25.5±0.9	10.0±3.2
A10	2-Cl	10.8±1.5	41.7±3.8	3.3±2.2	0	29.0±1.7
A11	2-Cl	4.1±5.6	64.9±4.3	4.7±1.1	2.7±2.5	25.7±3.3
A12	2-Cl	5.4±3.1	56.7±3.1	0.0±2.0	48.1±1.8	20.6±3.8
A13	2-Cl	3.6±3.0	58.2±4.1	0.0±2.0	32.6±1.4	4.4±4.1
A14	2-Cl	19.3±1.8	28.9±2.2	14.7±3.2	30.4±6.0	40.1±0.9
A15	4-Br	24.9±1.9	30.2±1.5	7.8±2.6	7.6±2.5	39.5±2.0
A16	4-Br	29.8±1.0	31.7±1.3	23.3±0.2	47.0±3.0	72.5±0.4
A17	3,4-Cl₂	10.9±0.9	0	8.6±2.0	11.4±2.0	0
A18	3,4-Cl₂	12.2±2.2	0	7.9±3.0	22.8±0.5	9.7±7.1
A19	3,4-Cl₂	5.1±2.2	33.3±2.7	4.6±6.0	13.9±4.5	20.0±6.8
A20	3,4-Cl₂	7.0±2.9	0.0±3.3	0.0±2.0	17.8±6.1	6.3±3.2
A21	3,4-Cl₂	0.6±2.9	0	6.0±2.0	5.0±4.4	0
A22	3,4-Cl₂	12.0±3.1	20.6±2.9	6.0±1.0	0	35.9±0.0
A23	4-CF₃	22.9±0.6	23.6±0.8	17.6±3.8	3.8±0.9	37.5±1.0
A24	4-CF₃	27.3±1.9	33.2±0.3	28.0±1.3	37.3±1.9	63.0±0.8
A25	4-OCH₃	21.4±2.8	21.1±2.9	7.3±0.9	11.4±1.7	47.0±1.0
A26	4-OCH₃	20.4±0.6	24.1±1.3	24.9±1.6	13.5±3.3	42.0±1.0
肟菌酯		43.9±1.5	68.6±0.6	2.0±0.0	49.7±0.5	69.8±1.8

Compd.	Fungus	Equation	r²
A7	T. cucumeris	y=0.96x+4.25	0.9890	6.02 (3.98~8.09)
A8	T. cucumeris	y=0.56x+4.9	0.9919	1.31 (0.00~4.86)
A16	T. cucumeris	y=0.50x+4.65	0.9939	5.01 (1.52~8.58)
Trifloxystrobin	T. cucumeris	y=0.57x+4.95	0.9918	1.13 (0.01~2.86)
A7	S. sclerotiorum	y=1.74x+2.91	0.9903	15.70 (13.39~18.58)
A8	S. sclerotiorum	y=1.40x+3.57	0.9710	10.62 (8.67~12.86)
Trifloxystrobin	S. sclerotiorum	y=0.53x+3.59	0.9970	38.09 (30.35~59.21)
A7	B. cinerea	y=1.32x+3.78	0.9263	8.25 (3.68~13.90)
Trifloxystrobin	B. cinerea	y=0.32x+4.14	0.9463	113.41 (60.30~771.46)

Compd.	Fungus	Equation	r²
A7	T. cucumeris	y=0.96x+4.25	0.9890	6.02 (3.98~8.09)
A8	T. cucumeris	y=0.56x+4.9	0.9919	1.31 (0.00~4.86)
A16	T. cucumeris	y=0.50x+4.65	0.9939	5.01 (1.52~8.58)
Trifloxystrobin	T. cucumeris	y=0.57x+4.95	0.9918	1.13 (0.01~2.86)
A7	S. sclerotiorum	y=1.74x+2.91	0.9903	15.70 (13.39~18.58)
A8	S. sclerotiorum	y=1.40x+3.57	0.9710	10.62 (8.67~12.86)
Trifloxystrobin	S. sclerotiorum	y=0.53x+3.59	0.9970	38.09 (30.35~59.21)
A7	B. cinerea	y=1.32x+3.78	0.9263	8.25 (3.68~13.90)
Trifloxystrobin	B. cinerea	y=0.32x+4.14	0.9463	113.41 (60.30~771.46)