Synthesis and Fungicidal Activity of Novel Butenolide Compounds Containing Oxime Ether Moiety

doi:10.6023/cjoc202203033

Abstract

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

Cite this article

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)

新型含肟醚结构丁烯内酯类化合物的合成及杀菌活性