含肟酯基L-香芹酮衍生物的设计、合成、晶体结构及杀菌活性

doi:10.6023/cjoc202010028

摘要/Abstract

L-香芹酮是一种具有杀菌活性的天然产物, 可用作新型杀菌剂的先导化合物. 因此, 以L-香芹酮为先导化合物,采用活性亚结构拼接法合成了一系列含肟酯的L-香芹酮衍生物. 化合物的结构经过红外, ¹H NMR, ¹³C NMR和高分辨质谱确认. 本研究还测定了这些化合物对油菜菌核真菌、小麦赤霉真菌、水稻稻瘟真菌、西瓜枯萎真菌和水稻纹枯真菌5种植物病原真菌的抑菌活性, 结果表明大部分化合物显示了良好的抑菌活性. 其中(E)-2-甲基-5-(丙-1-烯-2-基)环己-2-烯-1-酮O-(4-乙基苯甲酰基)肟(4e)对小麦赤霉的杀菌活性最好(EC₅₀=5.07 mg/L), (S,E)-2-甲基-5-(丙-1-烯-2-基)环己-2-烯-1-酮O-(3-甲基苯甲酰基)肟(4b)对油菜菌核的杀菌活性最好(EC₅₀=18.84 mg/L), 均优于对照药剂烯肟菌酯. 因此, L-香芹酮衍生物具有深入研究开发新型杀菌剂的潜力.

关键词: 天然产物, L-香芹酮, 合成, 杀菌活性

L-Carvone is a natural product with fungicidal activity, which can be used as a lead compound for screening new fungicides. A series of L-carvone derivatives containing an oxime ester moiety were synthesized by splicing active substructure strategy with L-carvone as the lead compound. The structures of the L-carvone derivatives were characterized by IR, ¹H NMR, ¹³C NMR and HRMS analyses. The antifungal activities of these compounds were evaluated against five plant pathogenic fungi, namely Sclerotinia sclerotiorum, Fusarium graminearum, Pyricularia grisea, Fusariwn oxysporum and Thanatephorus cucumeris. The results indicated that most of the compounds showed good antifungal activities. Among them, (E)-2- methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one O-(4-ethylbenzoyl)oxime (4e) had the best fungicidal activity against Fusarium graminearum (EC₅₀=5.07 mg/L), and (S,E)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one O-(3-methylbenzoyl)oxime (4b) had the best fungicidal activity against Sclerotinia sclerotiorum, (EC₅₀=18.84 mg/L), which were better than the commercial fungicide enestroburin. Therefore, L-carvone derivatives have the potential to develop new fungicides.

Key words: nature product, L-carvone, synthesis, fungicidal activity

引用此文

金灿, 邓希乐, 周勇, 周小毛. 含肟酯基L-香芹酮衍生物的设计、合成、晶体结构及杀菌活性[J]. 有机化学, 2021, 41(5): 2008-2018.

Can Jin, Xile Deng, Yong Zhou, Xiaomao Zhou. Design, Synthesis, Crystal Structure, and Fungicidal Activity of L-Carvone Derivatives Containing an Oxime Ester Moiety[J]. Chinese Journal of Organic Chemistry, 2021, 41(5): 2008-2018.

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参考文献 45

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Compd.	R	Inhibitory rate/%
Compd.	R	S. sclerotiorum	F. graminearum	P. grisea	F. oxysporum	T.cucumeris
4a	H	53.4	48.3	29.6	42.5	14.6
4b	3-CH₃	80.0	46.1	30.0	43.8	44.1
4c	4-CH₃	58.4	53.3	32.9	47.1	26.8
4d	2-CH₂CH₃	63.3	57.9	42.9	38.7	32.1
4e	4-CH₂CH₃	68.4	92.9	50.0	38.7	39.6
4f	4-CH(CH₃)₂	70.9	62.1	26.7	46.3	6.7
4g	4-C(CH₃)₃	57.1	62.9	33.3	46.2	22.1
4h	4-CH₂CH(CH₃)₂	39.1	69.6	28.8	45.6	10.5
4i	2-OCH₃	73.4	64.2	45.3	51.3	15.8
4j	3-OCH₃	41.2	66.7	30.8	38.8	11.7
4k	2-OCH₂CH₃	74.6	56.6	29.2	52.5	30.3
4l	4-OCH₂CH₃	62.9	83.3	31.7	57.5	10.4
4m	2-OCH₂CH₂CH₃	57.8	49.6	74.6	62.5	7.9
4n	2-Cl	45.3	48.8	28.3	47.5	7.8
4o	3-Cl	62.7	54.2	27.5	49.6	9.3
4p	4-Cl	41.6	82.9	36.7	44.1	10.4
4q	2,3-Cl	62.8	51.7	29.6	36.3	6.6
4r	2-Br	76.1	57.1	27.9	40.4	14.6
4s	3-Br	44.2	50.4	24.6	27.1	7.1
4t	4-Br	64.6	47.1	29.2	43.3	5.5
4u	2-F	58.3	67.5	28.7	38.3	20.4
4v	3-F	43.7	80.8	29.2	37.5	7.1
4w	4-F	44.6	83.1	42.1	51.7	11.7
4x	2,6-F	63.4	75.5	45.4	40.4	8.4
4y	4-CF₃	60.3	89.6	26.7	36.3	32.1
4z	4-NH₂	55.9	80.4	27.1	37.9	11.6
L-Carvone	—	32.9	57.7	22.3	35.3	8.3
Enestroburin	—	73.8	77.1	77.5	51.6	52.5

Compd.	R	Inhibitory rate/%
Compd.	R	S. sclerotiorum	F. graminearum	P. grisea	F. oxysporum	T.cucumeris
4a	H	53.4	48.3	29.6	42.5	14.6
4b	3-CH₃	80.0	46.1	30.0	43.8	44.1
4c	4-CH₃	58.4	53.3	32.9	47.1	26.8
4d	2-CH₂CH₃	63.3	57.9	42.9	38.7	32.1
4e	4-CH₂CH₃	68.4	92.9	50.0	38.7	39.6
4f	4-CH(CH₃)₂	70.9	62.1	26.7	46.3	6.7
4g	4-C(CH₃)₃	57.1	62.9	33.3	46.2	22.1
4h	4-CH₂CH(CH₃)₂	39.1	69.6	28.8	45.6	10.5
4i	2-OCH₃	73.4	64.2	45.3	51.3	15.8
4j	3-OCH₃	41.2	66.7	30.8	38.8	11.7
4k	2-OCH₂CH₃	74.6	56.6	29.2	52.5	30.3
4l	4-OCH₂CH₃	62.9	83.3	31.7	57.5	10.4
4m	2-OCH₂CH₂CH₃	57.8	49.6	74.6	62.5	7.9
4n	2-Cl	45.3	48.8	28.3	47.5	7.8
4o	3-Cl	62.7	54.2	27.5	49.6	9.3
4p	4-Cl	41.6	82.9	36.7	44.1	10.4
4q	2,3-Cl	62.8	51.7	29.6	36.3	6.6
4r	2-Br	76.1	57.1	27.9	40.4	14.6
4s	3-Br	44.2	50.4	24.6	27.1	7.1
4t	4-Br	64.6	47.1	29.2	43.3	5.5
4u	2-F	58.3	67.5	28.7	38.3	20.4
4v	3-F	43.7	80.8	29.2	37.5	7.1
4w	4-F	44.6	83.1	42.1	51.7	11.7
4x	2,6-F	63.4	75.5	45.4	40.4	8.4
4y	4-CF₃	60.3	89.6	26.7	36.3	32.1
4z	4-NH₂	55.9	80.4	27.1	37.9	11.6
L-Carvone	—	32.9	57.7	22.3	35.3	8.3
Enestroburin	—	73.8	77.1	77.5	51.6	52.5

Compd.	R	EC₅₀/(mg?L^–1)	R²	Regression equation	95% confidence limit
4e	4-CH₂CH₃	5.07	0.936	y=0.037x–0.187	0.32~8.65
4l	4-OCH₂CH₃	7.88	0.947	y=0.025x–0.200	1.47~12.61
4p	4-Cl	14.62	0.960	y=0.027x–0.392	9.87~18.89
4v	3-F	16.26	0.959	y=0.029x–0.469	12.03~20.28
4w	4-F	8.79	0.955	y=0.026x–0.225	2.67~13.41
4x	2,6-F	17.90	0.950	y=0.024x–0.437	13.02~22.69
4y	4-CF₃	7.92	0.946	y=0.033x–0.263	3.23~11.62
4z	4-NH₂	20.47	0.952	y=0.038x–0.786	9.56~34.50
Enestroburin	—	11.66	0.936	y=0.022x–0.261	5.23~16.73

Compd.	R	EC₅₀/(mg?L^–1)	R²	Regression equation	95% confidence limit
4e	4-CH₂CH₃	5.07	0.936	y=0.037x–0.187	0.32~8.65
4l	4-OCH₂CH₃	7.88	0.947	y=0.025x–0.200	1.47~12.61
4p	4-Cl	14.62	0.960	y=0.027x–0.392	9.87~18.89
4v	3-F	16.26	0.959	y=0.029x–0.469	12.03~20.28
4w	4-F	8.79	0.955	y=0.026x–0.225	2.67~13.41
4x	2,6-F	17.90	0.950	y=0.024x–0.437	13.02~22.69
4y	4-CF₃	7.92	0.946	y=0.033x–0.263	3.23~11.62
4z	4-NH₂	20.47	0.952	y=0.038x–0.786	9.56~34.50
Enestroburin	—	11.66	0.936	y=0.022x–0.261	5.23~16.73

Compd.	R	EC₅₀/(mg?L^–1)	R²	Regression equation	95% confidence limit
4b	3-CH₃	18.84	0.959	y=0.032x–0.595	9.45~28.84
4e	4-CH₂CH₃	26.11	0.949	y=0.025x–0.658	14.58~48.01
4f	4-CH(CH₃)₂	24.58	0.998	y=0.022x–0.551	16.29~31.17
4i	2-OCH₃	23.15	0.998	y=0.023x–0.529	17.33~25.50
4k	2-OCH₂CH₃	18.44	0.976	y=0.022x–0.411	13.11~29.07
4l	4-OCH₂CH₃	27.89	0.941	y=0.018x–0.500	20.84~36.84
4r	2-Br	25.34	0.995	y=0.023x–0.593	17.76~31.69
Enestroburin	—	23.31	0.961	y=0.029x–0.669	13.93~36.33